VCV000007237.61 - ClinVar

NM_000492.4(CFTR):c.4056G>C (p.Gln1352His)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Pathogenic (2); Likely pathogenic (2); Uncertain significance (11); Benign (1); Likely benign (3)

19 out of 23 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000492.4(CFTR):c.4056G>C (p.Gln1352His)

Variation ID: 7237 Accession: VCV000007237.61

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q31.2 7: 117664780 (GRCh38) [ NCBI UCSC ] 7: 117304834 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 6, 2016	Aug 22, 2026	Feb 2, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_000492.4:c.4056G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000483.3:p.Gln1352His	missense
NC_000007.14:g.117664780G>C
NC_000007.13:g.117304834G>C
NG_016465.4:g.203997G>C
LRG_663:g.203997G>C
LRG_663t1:c.4056G>C	LRG_663p1:p.Gln1352His

... more HGVS ... less HGVS

Protein change

Q1352H

Other names

Canonical SPDI

NC_000007.14:117664779:G:C

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00419 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.00419

1000 Genomes Project 30x 0.00359

Trans-Omics for Precision Medicine (TOPMed) 0.00061

Links

ClinGen: CA325616 OMIM: 602421.0133 dbSNP: rs113857788 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CFTR		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	3952	6466

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Cystic fibrosis	Conflicting classifications of pathogenicity (8)	criteria provided, conflicting classifications	Feb 2, 2026	RCV000007659.42
not provided	Uncertain significance (5)	criteria provided, multiple submitters, no conflicts	Oct 10, 2025	RCV000586028.33
CFTR-related disorder	Conflicting classifications of pathogenicity (4)	criteria provided, conflicting classifications	Jan 29, 2018	RCV001009487.22
not specified	Likely benign (1)	criteria provided, single submitter	Jun 26, 2025	RCV001375489.15
Bronchiectasis with or without elevated sweat chloride 1 Congenital bilateral aplasia of vas deferens from CFTR mutation Cystic fibrosis Hereditary pancreatitis	Conflicting classifications of pathogenicity (3)	criteria provided, conflicting classifications	Aug 27, 2024	RCV005031417.3
Congenital bilateral aplasia of vas deferens from CFTR mutation	Likely pathogenic (1)	criteria provided, single submitter	Feb 18, 2025	RCV006249551.3
Hereditary pancreatitis	Likely pathogenic (1)	criteria provided, single submitter	Nov 23, 2024	RCV006700667.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	CFTR-Related Disorders	Illumina Laboratory Services, Illumina Accession: SCV000466528.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (14) PubMed: 12952861‚ 15121783‚ 15463840‚ 16187186‚ 17003641‚ 17329263‚ 17539902‚ 19812525‚ 25492507‚ 26089335‚ 26199320‚ 26334177‚ 26708955‚ 9272157 Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (May 09, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV001713443.3 First in ClinVar: Jun 15, 2021 Last updated: Jan 26, 2024	Publications: PubMed (3) PubMed: 35753512‚ 36409994‚ 36437957 Comment: show PP3, PM3 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 5

Uncertain significance (Sep 28, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cystic fibrosis	Ambry Genetics Accession: SCV001183420.7 First in ClinVar: Mar 16, 2020 Last updated: Jan 11, 2026	Publications: PubMed (10) PubMed: 12952861‚ 15463840‚ 20558957‚ 25492507‚ 29216686‚ 29520692‚ 30811104‚ 30992994‚ 32352720‚ 9272157 Comment: show The p.Q1352H variant (also known as c.4056G>C), located in coding exon 25 of the CFTR gene, results from a G to C substitution at nucleotide position 4056. The glutamine at codon 1352 is replaced by histidine, an amino acid with highly similar properties. The variant has been reported in multiple Asian individuals with CFTR-related findings, including congenital absence of the vas deferens, chronic pancreatitis, and pulmonary disease cohorts; a few individuals were homozygotes and several had additional CFTR variants also detected (Dörk T et al. Hum. Genet., 1997 Sep;100:365-77; Anzai C et al. J. Cyst. Fibros., 2003 Mar;2:14-8; Lee JH et al. Hum. Mol. Genet., 2003 Sep;12:2321-32; Oka H et al. Intern Med, 2010 Jun;49:1251-2; Qiu L et al. Front Med, 2018 Oct;12:550-558; Iso M et al. Hum Genome Var, 2019 Apr;6:17; Yuan P et al. Andrology, 2019 05;7:329-340). In addition, in vitro functional studies showed that this variant results in a 70-80% reduction in the expression of the mature glycosylated CFTR protein and in chloride channel activity (Lee JH et al. Hum. Mol. Genet., 2003 Sep;12:2321-32). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on available evidence to date, this variant is unlikely to be causative of classic cystic fibrosis; however, its contribution to the development of a CFTR-related disorder is uncertain. Based on the available evidence, the clinical significance of this variant remains unclear. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Feb 02, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Cystic fibrosis	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000075079.13 First in ClinVar: Jul 03, 2013 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (Feb 18, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Congenital bilateral aplasia of vas deferens from CFTR mutation	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute Accession: SCV007097334.3 First in ClinVar: Nov 08, 2025 Last updated: Aug 04, 2026	Publications: PubMed (3) PubMed: 12952861‚ 30811104‚ 32777524 Comment: show This variant is classified as Likely pathogenic. Evidence in support of pathogenic classification: This variant has moderate functional evidence supporting abnormal protein function. Expression of mature glycosylated CFTR protein and whole cell chloride currents were significantly reduced in mutant cells (PMID: 12952861); Missense variant predicted to be damaging by in silico tool(s) or highly conserved with a major amino acid change. Additional information: Variant is predicted to result in a missense amino acid change from glutamine to histidine; This variant is heterozygous; This gene is associated with autosomal recessive disease; Variant is present in gnomAD >=0.01 and <0.03 for a recessive condition (v4: 912 heterozygote(s), 18 homozygote(s)). An alternate nucleotide change resulting in the same amino acid change is also present in gnomAD (v4: 68 heterozygote(s), 1 homozygote(s)); Alternative amino acid change(s) at the same position are present in gnomAD (Highest alelle count: v4: 17 heterozygote(s), 0 homozygote(s)); Previous reports of pathogenicity for this variant are conflicting. However, this variant has been reported in multiple individuals with CF-related disorders (LOVD; ClinVar; PMID: 30811104, 32777524); No comparable missense variants have previous evidence for pathogenicity; Variant is located in the annotated ABC transporter domain (PDB); Loss of function is a known mechanism of disease in this gene and is associated with cystic fibrosis (MIM#219700) and cystic fibrosis-related disorders; This variant has been shown to be maternally inherited by trio analysis. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Uncertain significance (May 28, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Cystic fibrosis	Mendelics Accession: SCV001137498.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Uncertain significance (Jun 22, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hereditary pancreatitis Bronchiectasis with or without elevated sweat chloride 1 Cystic fibrosis Congenital bilateral aplasia of vas deferens from CFTR mutation Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Fulgent Genetics, Fulgent Genetics Accession: SCV005666438.1 First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Nov 20, 2017) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not provided	Eurofins Ntd Llc (ga) Accession: SCV000331812.5 First in ClinVar: Dec 06, 2016 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 9 Zygosity: 9 Single Heterozygotes Sex: mixed

Likely benign (Jun 26, 2025) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not specified	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000696997.8 First in ClinVar: Mar 17, 2018 Last updated: Jul 05, 2025	Publications: PubMed (27) PubMed: 12952861‚ 15121783‚ 15463840‚ 16596947‚ 16678503‚ 17003641‚ 17329263‚ 17539902‚ 19812525‚ 20021716‚ 20233062‚ 20558957‚ 21520337‚ 22483971‚ 25492507‚ 28603918‚ 28608624‚ 29520692‚ 29997923‚ 31180159‚ 31682332‚ 32777524‚ 33374015‚ 33663443‚ 36335097‚ 38388235‚ 9272157 Comment: show Variant summary: CFTR c.4056G>C (p.Gln1352His) results in a non-conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function all suggest that this variant is likely to be disruptive. The variant allele was found at a frequency of 0.0023 in 1754570 control chromosomes, predominantly at a frequency of 0.019 within the East Asian subpopulation in the gnomAD database, including 16 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.47 fold of the estimated maximal expected allele frequency for a pathogenic variant in CFTR causing Non-Classic Cystic Fibrosis phenotype (0.013). Other control population data sources estimated the frequency of this variant to range from 0.019-0.022 across individuals of Chinese, Malay, Indian, and Japanese descent (Chan_2022, jMorp database), including >50 homozygotes. c.4056G>C variant is frequently reported in the simple heterozygous, presumed compound heterozygous, and homozygous states among numerous individuals with clinical features of CF-related conditions ranging from CBAVD and pancreatitis to cystic fibrosis, without strong evidence causality (example, Dork_1997, Keiles_2006, Bienvenu_2005, Xu_2017). However, one study reported the variant in two unaffected siblings who also carried a pathogenic CFTR mutation in trans (p.Y122X), including an apparently fertile male, suggesting the variant may not be fully penetrant or is not pathogenic (Bienvenu_2005). A recent study found the variant in 32/276 Chinese CAVD patients (i.e. with an allele frequency of 5.98%, including 1 homozygote), and in only 1 allele from 50 control individuals (Luo_2021). Several independent publications assert that this variant is possibly associated with these CF-related phenotypes based on elevated risk. However, none of the available evidence found any recorded instances of segregation with disease, nor did any of the case/control cohorts include statistically reliable risk data due to insufficient numbers of tested individuals. At least one publication reports experimental evidence evaluating an impact on protein function in vitro. The most pronounced variant effect results in 10%-30% of normal activity (Lee_2003) and approximately 36% of normal chloride channel conductance relative to wildtype (Bihler_2024). The following publications have been ascertained in the context of this evaluation (PMID: 15463840, 16596947, 38388235, 17539902, 28603918, 9272157, 15121783, 20021716, 29997923, 17003641, 33663443, 31180159, 12952861, 22483971, 32777524, 25492507, 16678503, 20558957, 29520692, 17329263, 33374015, 31682332, 21520337, 28608624, 19812525, 20233062, 36335097). ClinVar contains an entry for this variant (Variation ID: 7237). Based on the evidence outlined above, the variant was classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Mar 18, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cystic fibrosis	Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center Accession: SCV000267254.1 First in ClinVar: May 24, 2017 Last updated: May 24, 2017	Publications: PubMed (3) PubMed: 15121783‚ 16187186‚ 16678503 Observation: 1 Collection method: reference population Allele origin: germline Affected status: unknown more Observation 1 Collection method: reference population Allele origin: germline Affected status: unknown Number of individuals with the variant: 6 Age: 40-69 years Ethnicity/Population group: East Asian Geographic origin: South Korean

Likely benign (Sep 07, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cystic fibrosis	Johns Hopkins Genomics, Johns Hopkins University Accession: SCV001905498.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Publications: PubMed (4) PubMed: 12952861‚ 16187186‚ 16596947‚ 23514810 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (May 12, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cystic fibrosis	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002507388.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Aug 27, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Cystic fibrosis Bronchiectasis with or without elevated sweat chloride 1 Hereditary pancreatitis Congenital bilateral aplasia of vas deferens from CFTR mutation Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000603061.5 First in ClinVar: Dec 06, 2016 Last updated: Mar 11, 2025	Comment: show The CFTR c.4056G>C; p.Gln1352His variant (rs113857788) is reported in the literature in multiple individuals affected with CFTR-related disorders, including congenital bilateral absence of vas deferens (Anzai 2003, Danziger 2004, Ratbi 2007, Steiner 2011, Li 2012) and pancreatitis (Lee 2003, Keiles 2006). In multiple affected individuals, this variant has been found in trans to other pathogenic CFTR variants (Anzai 2003, Steiner 2011, Li 2012). This variant is also observed at a significantly higher frequency in Asian pancreatitis patients compared to unaffected individuals (Lee 2003, Fujiki 2004). This variant is reported in ClinVar (Variation ID: 7237) and is observed in the general population with an overall allele frequency of 0.1% (275/282620 alleles, including three homozygotes) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.923), and expression of the variant protein in a cell line reveals a significant reduction in mature CFTR protein detected compared to wildtype (Lee 2003). Based on available information, the variant is considered to be mildly pathogenic. References: Anzai C et al. CFTR gene mutations in Japanese individuals with congenital bilateral absence of the vas deferens. J Cyst Fibros. 2003 2(1):14-8. PMID: 15463840. Danziger K et al. Improved detection of cystic fibrosis mutations in infertility patients with DNA sequence analysis. Hum Reprod. 2004 19(3):540-6. PMID: 14998948. Fujiki K et al. Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis. J Med Genet. 2004 41(5):e55. PMID: 15121783. Keiles S et al. Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis. Pancreas. 2006 33(3):221-7. PMID: 17003641. Lee J et al. A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases. Hum Mol Genet. 2003 12(18):2321-32. PMID: 12952861. Li H et al. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) in Chinese patients with congenital bilateral absence of vas deferens. J Cyst Fibros. 2012 11(4):316-23. PMID: 22483971. Ratbi I et al. Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling. Hum Reprod. 2007 22(5):1285-91. PMID: 17329263. Steiner B et al. Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Hum Mutat. 2011 32(8):912-20. PMID: 21520337. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Jan 29, 2018) C Contributing to aggregate classification	criteria provided, single submitter (Claustres M et al. (Hum Mutat 2017))	CFTR-related disorders	CFTR-France Accession: SCV001169582.2 First in ClinVar: Mar 16, 2020 Last updated: Apr 13, 2025	Publications: PubMed (1) PubMed: 28603918 Observation: 2 Observation 1 Collection method: curation Allele origin: germline Affected status: yes Sex: male Observation 2 Collection method: curation Allele origin: germline Affected status: no Sex: female

Uncertain significance (Sep 24, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cystic fibrosis	Genesolutions, Medical Genetics Institutes, Ho Chi Minh City, Vietnam Accession: SCV006551337.1 First in ClinVar: Mar 28, 2026 Last updated: Mar 28, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Geographic origin: Vietnam

Uncertain significance (Oct 10, 2025) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV002538698.3 First in ClinVar: Jun 24, 2022 Last updated: Oct 25, 2025	Comment: show Although this variant has not been reported in the homozygous or compound heterozygous state in individuals with cystic fibrosis, it has been reported in individuals of Asian ancestry with CFTR-related disorders (PMID: 20021716, 21520337, 27578509, 32777524); Case control studies suggest this variant may be associated with pancreatitis in the Asian population; however, the association was not statistically significant in some studies (PMID: 15121783, 30992994, 25492507, 30420730); Published functional studies demonstrate a damaging effect: reduced chloride channel activity and chloride/bicarbonate exchange activity (PMID: 12952861); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27578509, 21520337, 16678503, 20981092, 20021716, 16187186, 30420730, 25492507, 17719933, 26089335, 28608624, 30450785, 28687971, 15121783, 31180159, 35119551, 23514810, 33663443, 32777524, 30992994, 38388235, 34931337, 35858753, 36437957, 35753512, 39107787, 40421383, 40065563, 39397452, 35313924, 39402445, 36335097, 12952861) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Uncertain significance (Oct 09, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Quest Diagnostics criteria)	not provided	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV002047115.4 First in ClinVar: Jan 03, 2022 Last updated: Dec 07, 2025	Publications: PubMed (61): PubMed: 12952861 15121783 15463840 16187186 16435054 16596947 16678503 17003641 17329263 17539902 18304229 19812525 20021716 20233062 20558957 21520337 21779199 22483971 23514810 25492507 26089335 26199320 26334177 26708955 27578509 28603918 28608624 28687971 29216686 29520692 29997923 30811104 30992994 31136843 31180159 31682332 32352720 32734384 32777524 33374015 33502066 33663443 34557648 34673937 34931337 35119551 35313924 35753512 35913788 36207272 36335097 36409994 36437957 36604502 36983403 37313453 38388235 39107787 39402445 40122225 9272157 Comment: show The CFTR c.4056G>C (p.Gln1352His) variant has been reported in the published literature in individuals described as having features of cystic fibrosis (CF) (PMIDs: 21779199 (2011), 26708955 (2016), 28608624 (2017), 31136843 (2019), 36409994 (2022), 39107787 (2024)). However, this variant is likely not associated with classic CF, but it may be associated with CFTR-related diseases such as congenital bilateral absence of the vas deferens (CBAVD) (PMIDs: 28603918 (2017), 30811104 (2019), 32777524 (2021), 34673937 (2021), 35119551 (2022), 39402445 (2024)), bronchiectasis (PMIDs: 12952861 (2003), 29997923 (2018)), and pancreatitis (PMIDs: 16187186 (2005), 32352720 (2020)). In addition, in vitro studies have reported that this variant has a moderate deleterious effect on CFTR protein expression and channel activity (PMID: 12952861 (2003), 38388235 (2024)). The frequency of this variant in the general population (Genome Aggregation Database, http://gnomad.broadinstitute.org) is higher than would generally be expected for pathogenic variants in this gene. Based on the available information, we are unable to determine the clinical significance of this variant. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Uncertain significance (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Bronchiectasis with or without elevated sweat chloride 1 Hereditary pancreatitis Congenital bilateral aplasia of vas deferens from CFTR mutation Cystic fibrosis Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Juno Genomics, Hangzhou Juno Genomics, Inc Accession: SCV007496004.1 First in ClinVar: Mar 01, 2026 Last updated: Mar 01, 2026	Comment: show Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.;For recessive disorders, detected in trans with a pathogenic variant.;Patient's phenotype or family history is highly specific for a disease with a single genetic etiology. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely pathogenic (Nov 23, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hereditary pancreatitis	Genetics and Genomic Medicine Centre, NeuroGen Healthcare, NeuroGen Healthcare Accession: SCV007602737.1 First in ClinVar: Jun 14, 2026 Last updated: Jun 14, 2026	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: yes Clinical Features: swollen pancreatitis (present) Age: 0-9 years Sex: female Ethnicity/Population group: South East Asian Geographic origin: Bangladesh Platform type: next-gen sequencing

Pathogenic (Sep 15, 2003) N Not contributing to aggregate classification	no assertion criteria provided	CYSTIC FIBROSIS	OMIM Accession: SCV000027860.3 First in ClinVar: Apr 04, 2013 Last updated: Apr 12, 2018	Publications: PubMed (1) PubMed: 12952861 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In a patient with cystic fibrosis (CF; 219700), Lee et al. (2003) identified a G-to-C transversion at nucleotide 4188 in exon 22 of the CFTR … (more) In a patient with cystic fibrosis (CF; 219700), Lee et al. (2003) identified a G-to-C transversion at nucleotide 4188 in exon 22 of the CFTR gene that resulted in a gln1352-to-his (Q1352H) amino acid change. (less)

Uncertain significance (Aug 29, 2024) N Not contributing to aggregate classification	no assertion criteria provided	CFTR-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004115982.3 First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024	Comment: show The CFTR c.4056G>C variant is predicted to result in the amino acid substitution p.Gln1352His. This variant has been reported in patients with several different phenotypes including asthma, alcoholic chronic pancreatitis, idiopathic chronic pancreatitis, azoospermic males, and bronchiectasis (Cho et al. 2016. PubMed ID: 27578509; Gallati et al. 2009. PubMed ID: 20021716; Kondo et al. 2015. PubMed ID: 26089335; Pall et al. 2007. PubMed ID: 17719933). The c.4056G>C (p.Gln1352His) variant has been found at higher rates in Asian patients with pancreatitis (12.3%) compared to unaffected controls (3.7%) (Fujiki et al. 2004. PubMed ID: 15121783). However, the majority of these studies were conducted in Eastern Asian population cohorts where the c.4056G>C variant is found at a higher allele frequency. Functional studies in CHO cell lines indicate the p.Gln1352His change decreases CFTR protein expression and chloride channel function (Lee et al. 2003. PubMed ID: 12952861; Fujiki et al. 2004. PubMed ID: 15121783; Ngiam et al. 2006. PubMed ID: 16678503). However, no family studies have been conducted to determine if the c.4056G>C variant segregates with disease in individual families and to our knowledge, no homozygous c.4056G>C individuals have been reported with a CFTR-related disorder. This variant has been observed with a minor allele frequency of ~1.3% in East Asians, including 3 homozygous individuals. The c.4056G>C has several conflicting interpretations in ClinVar ranging from benign to pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/7237). It is possible that the c.4056G>C variant exhibits incomplete penetrance or is a risk allele for disease. However, without additional conclusive evidence, the clinical significance of this variant remains uncertain. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (May 12, 2021) N Not contributing to aggregate classification	no assertion criteria provided	CFTR-related disorders	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002507474.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Mar 04, 2026) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Dasa Accession: SCV007667115.1 First in ClinVar: Aug 22, 2026 Last updated: Aug 22, 2026	Publications: PubMed (10) PubMed: 12952861‚ 15121783‚ 16678503‚ 17719933‚ 20021716‚ 26089335‚ 27578509‚ 28608624‚ 30811104‚ 32025909 Comment: show NM_000492.4(CFTR):c.4056G>C (p.Gln1352His) is a missense variant that results in the substitution of glutamine with histidine. This variant has been recurrently observed in individuals with CFTR-related disorders (PMID: 17719933; PMID: 20021716; PMID: 26089335; PMID: 27578509; PMID: 28608624). Functional evidence supports an impact on the gene or gene product. This classification is supported by population frequency inconsistent with a disease-causing role. Computational prediction algorithms are consistent with a deleterious effect. The currently available literature and clinical evidence are not sufficient to establish a definitive association between this variant and the reported condition. Therefore, this variant is classified as a variant of uncertain significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

The p.Q1352H variant (also known as c.4056G>C), located in coding exon 25 of the CFTR gene, results from a G to C substitution at nucleotide position 4056. The glutamine at codon 1352 is replaced by histidine, an amino acid with highly similar properties. The variant has been reported in multiple Asian individuals with CFTR-related findings, including congenital absence of the vas deferens, chronic pancreatitis, and pulmonary disease cohorts; a few individuals were homozygotes and several had additional CFTR variants also detected (Dörk T et al. Hum. Genet., 1997 Sep;100:365-77; Anzai C et al. J. Cyst. Fibros., 2003 Mar;2:14-8; Lee JH et al. Hum. Mol. Genet., 2003 Sep;12:2321-32; Oka H et al. Intern Med, 2010 Jun;49:1251-2; Qiu L et al. Front Med, 2018 Oct;12:550-558; Iso M et al. Hum Genome Var, 2019 Apr;6:17; Yuan P et al. Andrology, 2019 05;7:329-340). In addition, in vitro functional studies showed that this variant results in a 70-80% reduction in the expression of the mature glycosylated CFTR protein and in chloride channel activity (Lee JH et al. Hum. Mol. Genet., 2003 Sep;12:2321-32). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on available evidence to date, this variant is unlikely to be causative of classic cystic fibrosis; however, its contribution to the development of a CFTR-related disorder is uncertain. Based on the available evidence, the clinical significance of this variant remains unclear.

Comment:

This variant is classified as Likely pathogenic. Evidence in support of pathogenic classification: This variant has moderate functional evidence supporting abnormal protein function. Expression of mature glycosylated CFTR protein and whole cell chloride currents were significantly reduced in mutant cells (PMID: 12952861); Missense variant predicted to be damaging by in silico tool(s) or highly conserved with a major amino acid change. Additional information: Variant is predicted to result in a missense amino acid change from glutamine to histidine; This variant is heterozygous; This gene is associated with autosomal recessive disease; Variant is present in gnomAD >=0.01 and <0.03 for a recessive condition (v4: 912 heterozygote(s), 18 homozygote(s)). An alternate nucleotide change resulting in the same amino acid change is also present in gnomAD (v4: 68 heterozygote(s), 1 homozygote(s)); Alternative amino acid change(s) at the same position are present in gnomAD (Highest alelle count: v4: 17 heterozygote(s), 0 homozygote(s)); Previous reports of pathogenicity for this variant are conflicting. However, this variant has been reported in multiple individuals with CF-related disorders (LOVD; ClinVar; PMID: 30811104, 32777524); No comparable missense variants have previous evidence for pathogenicity; Variant is located in the annotated ABC transporter domain (PDB); Loss of function is a known mechanism of disease in this gene and is associated with cystic fibrosis (MIM#219700) and cystic fibrosis-related disorders; This variant has been shown to be maternally inherited by trio analysis.

Comment:

Variant summary: CFTR c.4056G>C (p.Gln1352His) results in a non-conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function all suggest that this variant is likely to be disruptive. The variant allele was found at a frequency of 0.0023 in 1754570 control chromosomes, predominantly at a frequency of 0.019 within the East Asian subpopulation in the gnomAD database, including 16 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.47 fold of the estimated maximal expected allele frequency for a pathogenic variant in CFTR causing Non-Classic Cystic Fibrosis phenotype (0.013). Other control population data sources estimated the frequency of this variant to range from 0.019-0.022 across individuals of Chinese, Malay, Indian, and Japanese descent (Chan_2022, jMorp database), including >50 homozygotes. c.4056G>C variant is frequently reported in the simple heterozygous, presumed compound heterozygous, and homozygous states among numerous individuals with clinical features of CF-related conditions ranging from CBAVD and pancreatitis to cystic fibrosis, without strong evidence causality (example, Dork_1997, Keiles_2006, Bienvenu_2005, Xu_2017). However, one study reported the variant in two unaffected siblings who also carried a pathogenic CFTR mutation in trans (p.Y122X), including an apparently fertile male, suggesting the variant may not be fully penetrant or is not pathogenic (Bienvenu_2005). A recent study found the variant in 32/276 Chinese CAVD patients (i.e. with an allele frequency of 5.98%, including 1 homozygote), and in only 1 allele from 50 control individuals (Luo_2021). Several independent publications assert that this variant is possibly associated with these CF-related phenotypes based on elevated risk. However, none of the available evidence found any recorded instances of segregation with disease, nor did any of the case/control cohorts include statistically reliable risk data due to insufficient numbers of tested individuals. At least one publication reports experimental evidence evaluating an impact on protein function in vitro. The most pronounced variant effect results in 10%-30% of normal activity (Lee_2003) and approximately 36% of normal chloride channel conductance relative to wildtype (Bihler_2024). The following publications have been ascertained in the context of this evaluation (PMID: 15463840, 16596947, 38388235, 17539902, 28603918, 9272157, 15121783, 20021716, 29997923, 17003641, 33663443, 31180159, 12952861, 22483971, 32777524, 25492507, 16678503, 20558957, 29520692, 17329263, 33374015, 31682332, 21520337, 28608624, 19812525, 20233062, 36335097). ClinVar contains an entry for this variant (Variation ID: 7237). Based on the evidence outlined above, the variant was classified as likely benign.

Comment:

The CFTR c.4056G>C; p.Gln1352His variant (rs113857788) is reported in the literature in multiple individuals affected with CFTR-related disorders, including congenital bilateral absence of vas deferens (Anzai 2003, Danziger 2004, Ratbi 2007, Steiner 2011, Li 2012) and pancreatitis (Lee 2003, Keiles 2006). In multiple affected individuals, this variant has been found in trans to other pathogenic CFTR variants (Anzai 2003, Steiner 2011, Li 2012). This variant is also observed at a significantly higher frequency in Asian pancreatitis patients compared to unaffected individuals (Lee 2003, Fujiki 2004). This variant is reported in ClinVar (Variation ID: 7237) and is observed in the general population with an overall allele frequency of 0.1% (275/282620 alleles, including three homozygotes) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.923), and expression of the variant protein in a cell line reveals a significant reduction in mature CFTR protein detected compared to wildtype (Lee 2003). Based on available information, the variant is considered to be mildly pathogenic. References: Anzai C et al. CFTR gene mutations in Japanese individuals with congenital bilateral absence of the vas deferens. J Cyst Fibros. 2003 2(1):14-8. PMID: 15463840. Danziger K et al. Improved detection of cystic fibrosis mutations in infertility patients with DNA sequence analysis. Hum Reprod. 2004 19(3):540-6. PMID: 14998948. Fujiki K et al. Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis. J Med Genet. 2004 41(5):e55. PMID: 15121783. Keiles S et al. Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis. Pancreas. 2006 33(3):221-7. PMID: 17003641. Lee J et al. A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases. Hum Mol Genet. 2003 12(18):2321-32. PMID: 12952861. Li H et al. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) in Chinese patients with congenital bilateral absence of vas deferens. J Cyst Fibros. 2012 11(4):316-23. PMID: 22483971. Ratbi I et al. Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling. Hum Reprod. 2007 22(5):1285-91. PMID: 17329263. Steiner B et al. Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Hum Mutat. 2011 32(8):912-20. PMID: 21520337.

Comment:

Although this variant has not been reported in the homozygous or compound heterozygous state in individuals with cystic fibrosis, it has been reported in individuals of Asian ancestry with CFTR-related disorders (PMID: 20021716, 21520337, 27578509, 32777524); Case control studies suggest this variant may be associated with pancreatitis in the Asian population; however, the association was not statistically significant in some studies (PMID: 15121783, 30992994, 25492507, 30420730); Published functional studies demonstrate a damaging effect: reduced chloride channel activity and chloride/bicarbonate exchange activity (PMID: 12952861); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27578509, 21520337, 16678503, 20981092, 20021716, 16187186, 30420730, 25492507, 17719933, 26089335, 28608624, 30450785, 28687971, 15121783, 31180159, 35119551, 23514810, 33663443, 32777524, 30992994, 38388235, 34931337, 35858753, 36437957, 35753512, 39107787, 40421383, 40065563, 39397452, 35313924, 39402445, 36335097, 12952861)

Comment:

The CFTR c.4056G>C (p.Gln1352His) variant has been reported in the published literature in individuals described as having features of cystic fibrosis (CF) (PMIDs: 21779199 (2011), 26708955 (2016), 28608624 (2017), 31136843 (2019), 36409994 (2022), 39107787 (2024)). However, this variant is likely not associated with classic CF, but it may be associated with CFTR-related diseases such as congenital bilateral absence of the vas deferens (CBAVD) (PMIDs: 28603918 (2017), 30811104 (2019), 32777524 (2021), 34673937 (2021), 35119551 (2022), 39402445 (2024)), bronchiectasis (PMIDs: 12952861 (2003), 29997923 (2018)), and pancreatitis (PMIDs: 16187186 (2005), 32352720 (2020)). In addition, in vitro studies have reported that this variant has a moderate deleterious effect on CFTR protein expression and channel activity (PMID: 12952861 (2003), 38388235 (2024)). The frequency of this variant in the general population (Genome Aggregation Database, http://gnomad.broadinstitute.org) is higher than would generally be expected for pathogenic variants in this gene. Based on the available information, we are unable to determine the clinical significance of this variant.

Comment:

Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.;For recessive disorders, detected in trans with a pathogenic variant.;Patient's phenotype or family history is highly specific for a disease with a single genetic etiology.

Comment:

The CFTR c.4056G>C variant is predicted to result in the amino acid substitution p.Gln1352His. This variant has been reported in patients with several different phenotypes including asthma, alcoholic chronic pancreatitis, idiopathic chronic pancreatitis, azoospermic males, and bronchiectasis (Cho et al. 2016. PubMed ID: 27578509; Gallati et al. 2009. PubMed ID: 20021716; Kondo et al. 2015. PubMed ID: 26089335; Pall et al. 2007. PubMed ID: 17719933). The c.4056G>C (p.Gln1352His) variant has been found at higher rates in Asian patients with pancreatitis (12.3%) compared to unaffected controls (3.7%) (Fujiki et al. 2004. PubMed ID: 15121783). However, the majority of these studies were conducted in Eastern Asian population cohorts where the c.4056G>C variant is found at a higher allele frequency. Functional studies in CHO cell lines indicate the p.Gln1352His change decreases CFTR protein expression and chloride channel function (Lee et al. 2003. PubMed ID: 12952861; Fujiki et al. 2004. PubMed ID: 15121783; Ngiam et al. 2006. PubMed ID: 16678503). However, no family studies have been conducted to determine if the c.4056G>C variant segregates with disease in individual families and to our knowledge, no homozygous c.4056G>C individuals have been reported with a CFTR-related disorder. This variant has been observed with a minor allele frequency of ~1.3% in East Asians, including 3 homozygous individuals. The c.4056G>C has several conflicting interpretations in ClinVar ranging from benign to pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/7237). It is possible that the c.4056G>C variant exhibits incomplete penetrance or is a risk allele for disease. However, without additional conclusive evidence, the clinical significance of this variant remains uncertain.

Comment:

NM_000492.4(CFTR):c.4056G>C (p.Gln1352His) is a missense variant that results in the substitution of glutamine with histidine. This variant has been recurrently observed in individuals with CFTR-related disorders (PMID: 17719933; PMID: 20021716; PMID: 26089335; PMID: 27578509; PMID: 28608624). Functional evidence supports an impact on the gene or gene product. This classification is supported by population frequency inconsistent with a disease-causing role. Computational prediction algorithms are consistent with a deleterious effect. The currently available literature and clinical evidence are not sufficient to establish a definitive association between this variant and the reported condition. Therefore, this variant is classified as a variant of uncertain significance.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Genetic syndromes leading to male infertility: a systematic review.	Cheng LG	Fertility and sterility	2025	PMID: 40122225
Genetic diagnosis and outcomes of intracytoplasmic sperm injection in South Chinese patients with congenital bilateral aplasia of the vas deferens.	Hu H	Basic and clinical andrology	2024	PMID: 39402445
Compound heterozygous CFTR variants (Q1352H and 5T; TG13) in a Chinese patient with cystic fibrosis.	Guo R	Diagnostic pathology	2024	PMID: 39107787
In vitro modulator responsiveness of 655 CFTR variants found in people with cystic fibrosis.	Bihler H	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2024	PMID: 38388235
A comprehensive review of cystic fibrosis in Africa and Asia.	Abubakar Bobbo K	Saudi journal of biological sciences	2023	PMID: 37313453
The Association between CFTR Gene Mutation Heterozygosity and Asthma Development: A Systematic Review.	Koumpagioti D	Journal of clinical medicine	2023	PMID: 36983403
Correlation between CFTR variants and outcomes of ART in patients with CAVD in Central China.	Qu X	Scientific reports	2023	PMID: 36604502
Cystic Fibrosis Screen Positive, Inconclusive Diagnosis Genotypes in People with Cystic Fibrosis from the U.S. Patient Registry.	Salinas DB	Annals of the American Thoracic Society	2023	PMID: 36409994
Congenital absence of the vas deferens with hypospadias or without hypospadias: Phenotypic findings and genetic considerations.	Fang J	Frontiers in genetics	2022	PMID: 36437957
Analysis of clinically relevant variants from ancestrally diverse Asian genomes.	Chan SH	Nature communications	2022	PMID: 36335097
ECFS standards of care on CFTR-related disorders: Diagnostic criteria of CFTR dysfunction.	Sermet-Gaudelus I	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2022	PMID: 36207272
Heterogeneous spectrum of CFTR gene mutations in Chinese patients with CAVD and the dilemma of genetic blocking strategy.	Feng J	Reproduction (Cambridge, England)	2022	PMID: 35913788
Clinical exome sequencing of 1000 families with complex immune phenotypes: Toward comprehensive genomic evaluations.	Similuk MN	The Journal of allergy and clinical immunology	2022	PMID: 35753512
Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians.	Ni Q	Orphanet journal of rare diseases	2022	PMID: 35313924
Genetic analysis and intracytoplasmic sperm injection outcomes of Chinese patients with congenital bilateral absence of vas deferens.	Cheng H	Journal of assisted reproduction and genetics	2022	PMID: 35119551
Mutations in CFTR genes are associated with oligoasthenospermia in infertile men undergoing IVF.	Li Q	Andrologia	2022	PMID: 34931337
Genetic mutation analysis of 22 patients with congenital absence of vas deferens: a single-center study†.	Tan MQ	Biology of reproduction	2022	PMID: 34673937
A review of cystic fibrosis: Basic and clinical aspects.	Chen Q	Animal models and experimental medicine	2021	PMID: 34557648
Etiologic distribution and clinical characteristics of pediatric diabetes in 276 children and adolescents with diabetes at a single academic center.	Kim JH	BMC pediatrics	2021	PMID: 33663443
A data set of variants derived from 1455 clinical and research exomes is efficient in variant prioritization for early-onset monogenic disorders in Indians.	Kausthubham N	Human mutation	2021	PMID: 33502066
Andrological findings in infertile men with two (biallelic) CFTR mutations: results of a multicentre study in Germany and Austria comprising 71 patients.	Rudnik-Schöneborn S	Human reproduction (Oxford, England)	2021	PMID: 33374015
Mutation analysis of the cystic fibrosis transmembrane conductance regulator gene in Chinese congenital absence of vas deferens patients.	Luo S	Gene	2021	PMID: 32777524
Genomic, transcriptomic, and protein landscape profile of CFTR and cystic fibrosis.	Sanders M	Human genetics	2021	PMID: 32734384
Genetics of the congenital absence of the vas deferens.	Bieth E	Human genetics	2021	PMID: 32025909
Disordered Gut Microbiota in Children Who Have Chronic Pancreatitis and Different Functional Gene Mutations.	Wang W	Clinical and translational gastroenterology	2020	PMID: 32352720
Cystic fibrosis newborn screening in Denmark: Experience from the first 2 years.	Skov M	Pediatric pulmonology	2020	PMID: 31682332
A Vietnamese human genetic variation database.	Le VS	Human mutation	2019	PMID: 31180159
Deletion of exons 16-17b of CFTR is frequently identified in Korean patients with cystic fibrosis.	Sohn YB	European journal of medical genetics	2019	PMID: 31136843
The CFTR gene variants in Japanese children with idiopathic pancreatitis.	Iso M	Human genome variation	2019	PMID: 30992994
Expanding the phenotypic and genetic spectrum of Chinese patients with congenital absence of vas deferens bearing CFTR and ADGRG2 alleles.	Yuan P	Andrology	2019	PMID: 30811104
Next-generation sequencing for identifying genetic mutations in adults with bronchiectasis.	Guan WJ	Journal of thoracic disease	2018	PMID: 29997923
Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis.	Qiu L	Frontiers of medicine	2018	PMID: 29520692
Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: reproductive implications and genetic counseling.	de Souza DAS	Andrology	2018	PMID: 29216686
The spectrum of genetic variants in hereditary pancreatic cancer includes Fanconi anemia genes.	Slavin TP	Familial cancer	2018	PMID: 28687971
Four case reports of Chinese cystic fibrosis patients and literature review.	Xu J	Pediatric pulmonology	2017	PMID: 28608624
CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants.	Claustres M	Human mutation	2017	PMID: 28603918
PRSS1, SPINK1, CFTR, and CTRC Pathogenic Variants in Korean Patients With Idiopathic Pancreatitis.	Cho SM	Annals of laboratory medicine	2016	PMID: 27578509
The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing.	Schrijver I	The Journal of molecular diagnostics : JMD	2016	PMID: 26708955
Utility of whole-genome sequencing for detection of newborn screening disorders in a population cohort of 1,696 neonates.	Bodian DL	Genetics in medicine : official journal of the American College of Medical Genetics	2016	PMID: 26334177
Low-frequency germline variants across 6p22.2-6p21.33 are associated with non-obstructive azoospermia in Han Chinese men.	Ni B	Human molecular genetics	2015	PMID: 26199320
Functional characteristics of L1156F-CFTR associated with alcoholic chronic pancreatitis in Japanese.	Kondo S	American journal of physiology. Gastrointestinal and liver physiology	2015	PMID: 26089335
Targeted next-generation sequencing effectively analyzed the cystic fibrosis transmembrane conductance regulator gene in pancreatitis.	Nakano E	Digestive diseases and sciences	2015	PMID: 25492507
Association of CFTR gene variants with nontuberculous mycobacterial lung disease in a Korean population with a low prevalence of cystic fibrosis.	Jang MA	Journal of human genetics	2013	PMID: 23514810
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) in Chinese patients with congenital bilateral absence of vas deferens.	Li H	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2012	PMID: 22483971
Heterogeneous spectrum of CFTR gene mutations in Korean patients with cystic fibrosis.	Jung H	The Korean journal of laboratory medicine	2011	PMID: 21779199
Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens.	Steiner B	Human mutation	2011	PMID: 21520337
A Japanese adult case of forme fruste cystic fibrosis.	Oka H	Internal medicine (Tokyo, Japan)	2010	PMID: 20558957
Distribution of CFTR variations in an Indonesian enteric fever cohort.	van de Vosse E	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America	2010	PMID: 20233062
Independent contribution of common CFTR variants to chronic pancreatitis.	de Cid R	Pancreas	2010	PMID: 19812525
Cystic fibrosis transmembrane conductance regulator mutations in azoospermic and oligospermic men and their partners.	Gallati S	Reproductive biomedicine online	2009	PMID: 20021716
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation associated with a congenital bilateral absence of vas deferens.	Sakamoto H	International journal of urology : official journal of the Japanese Urological Association	2008	PMID: 18304229
Primary sclerosing cholangitis in childhood is associated with abnormalities in cystic fibrosis-mediated chloride channel function.	Pall H	The Journal of pediatrics	2007	PMID: 17719933
Spectrum of mutations and variants/haplotypes of CFTR and genotype-phenotype correlation in idiopathic chronic pancreatitis and controls in Chinese by complete analysis.	Chang MC	Clinical genetics	2007	PMID: 17539902
Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling.	Ratbi I	Human reproduction (Oxford, England)	2007	PMID: 17329263
Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis.	Keiles S	Pancreas	2006	PMID: 17003641
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asians with chronic pulmonary disease: a pilot study.	Ngiam NS	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2006	PMID: 16678503
Detection of F508del mutation in cystic fibrosis transmembrane conductance regulator gene mutation among Malays.	Zilfalil BA	Singapore medical journal	2006	PMID: 16435054
Spectrum of CFTR mutations on Réunion Island: impact on neonatal screening.	Bienvenu T	Human biology	2005	PMID: 16596947
Mutation analysis of SPINK1 and CFTR gene in Korean patients with alcoholic chronic pancreatitis.	Lee KH	Digestive diseases and sciences	2005	PMID: 16187186
Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis.	Fujiki K	Journal of medical genetics	2004	PMID: 15121783
CFTR gene mutations in Japanese individuals with congenital bilateral absence of the vas deferens.	Anzai C	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2003	PMID: 15463840
A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases.	Lee JH	Human molecular genetics	2003	PMID: 12952861
Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens.	Dörk T	Human genetics	1997	PMID: 9272157
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR	-	-	-	-
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Text-mined citations for rs113857788 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 22, 2026