VCV000053213.9 - ClinVar

NM_000492.4(CFTR):c.1203G>A (p.Trp401Ter)

Germline

Reviewed by expert panel

Reviewed by expert panel. Learn more about how ClinVar calculates review status.

Pathogenic

for Cystic fibrosis

Classification is based on the expert panel submission

Mar 2017 by CFTR2

The classification 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.1203G>A (p.Trp401Ter)

Variation ID: 53213 Accession: VCV000053213.9

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q31.2 7: 117542102 (GRCh38) [ NCBI UCSC ] 7: 117182156 (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	Jan 6, 2018	Feb 23, 2026	Mar 17, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_000492.4:c.1203G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000483.3:p.Trp401Ter	nonsense
NC_000007.14:g.117542102G>A
NC_000007.13:g.117182156G>A
NG_016465.4:g.81319G>A
LRG_663:g.81319G>A
LRG_663t1:c.1203G>A	LRG_663p1:p.Trp401Ter

... more HGVS ... less HGVS

Protein change

W401*

Other names

Canonical SPDI

NC_000007.14:117542101:G:A

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.

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

Links

ClinGen: CA328083 dbSNP: rs397508175 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	3800	6217

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	Pathogenic (4)	reviewed by expert panel	Mar 17, 2017	RCV000056344.14
CFTR-related disorder	Pathogenic (1)	no assertion criteria provided	Mar 17, 2017	RCV001831721.1

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.
Pathogenic (Mar 17, 2017) C Contributing to aggregate classification	reviewed by expert panel (Sosnay PR et al. (Nat Genet 2013))	Cystic fibrosis	CFTR2 Study: CFTR2 Accession: SCV000087506.4 First in ClinVar: Oct 18, 2013 Last updated: Jan 06, 2018	Other databases https://cftr2.org https://cftr2.org Observation: 1 Collection method: research Allele origin: germline Affected status: yes Observation 1 Collection method: research Allele origin: germline Affected status: yes

Pathogenic (May 18, 2022) N Not contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Cystic fibrosis	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003011447.4 First in ClinVar: Feb 07, 2023 Last updated: Feb 23, 2026	Publications: PubMed (5) PubMed: 1695717‚ 23974870‚ 7508414‚ 7691345‚ 9725922 Comment: show For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 53213). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 7508414, 23974870). This variant is present in population databases (rs397508175, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Trp401*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). (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) N Not contributing to aggregate classification	criteria provided, single submitter (Claustres M et al. (Hum Mutat 2017))	cystic fibrosis	CFTR-France Accession: SCV001169445.1 First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020	Publications: PubMed (1) PubMed: 28603918 Observation: 1 Collection method: curation Allele origin: germline Affected status: yes Observation 1 Collection method: curation Allele origin: germline Affected status: yes

Pathogenic (Apr 03, 2015) N Not contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cystic fibrosis	Ambry Genetics Accession: SCV002651686.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (1) PubMed: 23974870 Comment: show The p.W401* pathogenic mutation (also known as c.1203G>A), located in coding exon 9 of the CFTR gene, results from a G to A substitution at nucleotide position 1203. This changes the amino acid from a tryptophan to a stop codon within coding exon 9. This pathogenic mutation is associated with elevated sweat chloride levels, pancreatic insufficiency (PI), and decreased lung function (Sosnay PR et al. Nat Genet. 2013;45(10):1160-7, Supplementary Table and The Clinical and Functional Translation of CFTR (CFTR2); available at http://cftr2.org. Accessed April 2, 2015). In addition to the clinical data available in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). (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 (Mar 17, 2017) N Not contributing to aggregate classification	no assertion criteria provided	CFTR-related disorders	Natera, Inc. Accession: SCV002080556.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 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

Comment:

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 53213). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 7508414, 23974870). This variant is present in population databases (rs397508175, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Trp401*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922).

Comment:

The p.W401* pathogenic mutation (also known as c.1203G>A), located in coding exon 9 of the CFTR gene, results from a G to A substitution at nucleotide position 1203. This changes the amino acid from a tryptophan to a stop codon within coding exon 9. This pathogenic mutation is associated with elevated sweat chloride levels, pancreatic insufficiency (PI), and decreased lung function (Sosnay PR et al. Nat Genet. 2013;45(10):1160-7, Supplementary Table and The Clinical and Functional Translation of CFTR (CFTR2); available at http://cftr2.org. Accessed April 2, 2015). In addition to the clinical data available in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene.	Sosnay PR	Nature genetics	2013	PMID: 23974870
Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis.	Cohn JA	The New England journal of medicine	1998	PMID: 9725922
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR.	Yang Y	Human molecular genetics	1993	PMID: 7691345
Detection of 98.5% of the mutations in 200 Belgian cystic fibrosis alleles by reverse dot-blot and sequencing of the complete coding region and exon/intron junctions of the CFTR gene.	Cuppens H	Genomics	1993	PMID: 7508414
A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.	Cutting GR	Nature	1990	PMID: 1695717
https://cftr2.org	-	-	-	-

Text-mined citations for rs397508175 ...

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 Mar 14, 2026