VCV000000851.6 - ClinVar

NM_080669.6(SLC46A1):c.194del (p.Gly65fs)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

1 out of 3 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_080669.6(SLC46A1):c.194del (p.Gly65fs)

Variation ID: 851 Accession: VCV000000851.6

Type and length

Deletion, 1 bp

Location

Cytogenetic: 17q11.2 17: 28405921 (GRCh38) [ NCBI UCSC ] 17: 26732939 (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	Apr 4, 2013	Feb 23, 2026	Sep 11, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_080669.6:c.194del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_542400.2:p.Gly65fs	frameshift
NM_001242366.3:c.194del	NP_001229295.1:p.Gly65fs	frameshift
NC_000017.11:g.28405927del
NC_000017.10:g.26732945del
NG_013306.1:g.5290del
LRG_183:g.5290del
LRG_183t1:c.194del	LRG_183p1:p.Gly65Alafs

... more HGVS ... less HGVS

Protein change

G65fs

Other names

Canonical SPDI

NC_000017.11:28405920:CCCCCCC:CCCCCC

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: CA026500 OMIM: 611672.0002 dbSNP: rs80338769 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.
SLC46A1		-	-	GRCh38 GRCh37	220	428

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.
Congenital defect of folate absorption	Pathogenic (2)	no assertion criteria provided	Aug 15, 2007	RCV000000899.5
not provided	Pathogenic (1)	criteria provided, single submitter	Sep 11, 2023	RCV003555883.4

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 (Sep 11, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004298191.3 First in ClinVar: Feb 14, 2024 Last updated: Feb 23, 2026	Publications: PubMed (2) PubMed: 17446347‚ 21333572 Comment: show This sequence change creates a premature translational stop signal (p.Gly65Alafs*25) in the SLC46A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC46A1 are known to be pathogenic (PMID: 17446347, 21333572). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with hereditary folate malabsorption (PMID: 17446347). ClinVar contains an entry for this variant (Variation ID: 851). For these reasons, this variant has been classified as Pathogenic. (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 (Aug 15, 2007) N Not contributing to aggregate classification	no assertion criteria provided	FOLATE MALABSORPTION, HEREDITARY	OMIM Accession: SCV000021049.2 First in ClinVar: Apr 04, 2013 Last updated: Sep 14, 2013	Publications: PubMed (1) PubMed: 17446347 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 an African American boy with hereditary folate malabsorption (229050), Zhao et al. (2007) identified a homozygous 1-bp deletion (194delG) in the SLC46A1 gene, resulting … (more) In an African American boy with hereditary folate malabsorption (229050), Zhao et al. (2007) identified a homozygous 1-bp deletion (194delG) in the SLC46A1 gene, resulting in a frameshift and premature termination. In vitro functional expression studies showed that the mutant protein had no folate transport activity. (less)

not provided (-) N Not contributing to aggregate classification	no classification provided	Congenital defect of folate absorption	GeneReviews Accession: SCV000041571.2 First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022	Publications: PubMed (2) PubMed: 17446347‚ 20301716 BookShelf: NBK1673 BookShelf: NBK1673 Observation: 1 Collection method: literature only Allele origin: unknown Affected status: not provided Observation 1 Collection method: literature only Allele origin: unknown Affected status: not provided

Comment:

This sequence change creates a premature translational stop signal (p.Gly65Alafs*25) in the SLC46A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC46A1 are known to be pathogenic (PMID: 17446347, 21333572). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with hereditary folate malabsorption (PMID: 17446347). ClinVar contains an entry for this variant (Variation ID: 851). For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Hereditary Folate Malabsorption.	Adam MP	-	2026	PMID: 20301716
Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption.	Shin DS	Molecular genetics and metabolism	2011	PMID: 21333572
The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption.	Zhao R	Blood	2007	PMID: 17446347

Text-mined citations for rs80338769 ...

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 Apr 13, 2026