VCV000030925.2 - ClinVar

NM_080669.6(SLC46A1):c.1012G>C (p.Gly338Arg)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

1 out of 2 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.1012G>C (p.Gly338Arg)

Variation ID: 30925 Accession: VCV000030925.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q11.2 17: 26731703 (GRCh37) [ NCBI UCSC ] 17: 28404685 (GRCh38) [ 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	Oct 31, 2013	May 1, 2011

HGVS

Nucleotide	Protein	Molecular consequence
NM_080669.6:c.1012G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_542400.2:p.Gly338Arg	missense
NM_001242366.3:c.1012G>C	NP_001229295.1:p.Gly338Arg	missense
NC_000017.11:g.28404685C>G
NC_000017.10:g.26731703C>G
NG_013306.1:g.6526G>C
LRG_183:g.6526G>C
LRG_183t1:c.1012G>C
	Q96NT5:p.Gly338Arg

... more HGVS ... less HGVS

Protein change

G338R

Other names

Canonical SPDI

NC_000017.11:28404684:C:G

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: CA026494 UniProtKB: Q96NT5#VAR_067962 UniProtKB/Swiss-Prot: VAR_067962 OMIM: 611672.0010 dbSNP: rs281875209 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 (1)	no assertion criteria provided	May 1, 2011	RCV000023913.3
not provided	not provided (1)	no classification provided	-	RCV000059709.1

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 (May 01, 2011) C Contributing to aggregate classification	no assertion criteria provided	FOLATE MALABSORPTION, HEREDITARY	OMIM Accession: SCV000045204.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (1) PubMed: 21333572 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 8-year-old Tunisian boy, born of consanguineous parents, with hereditary folate malabsorption (229050), Shin et al. (2011) identified a homozygous 1012G-C transversion in the … (more) In an 8-year-old Tunisian boy, born of consanguineous parents, with hereditary folate malabsorption (229050), Shin et al. (2011) identified a homozygous 1012G-C transversion in the SLC46A1 gene, resulting in a gly338-to-arg (G338R) substitution in the ninth transmembrane domain. In vitro functional expression assays in Hela cells showed that the mutant protein was inactive with no folate uptake activity. The patient developed macrocytic anemia with low serum folate at age 2.5 months. He was treated with leucovorin, which corrected the anemia and axial hypertonia. EEG and head CT scan were normal. Two affected sibs had died. (less)

not provided (-) N Not contributing to aggregate classification	no classification provided	not provided	UniProtKB/Swiss-Prot Accession: SCV000091279.1 First in ClinVar: Oct 31, 2013 Last updated: Oct 31, 2013	Observation: 1 Collection method: not provided Allele origin: not provided Affected status: not provided Observation 1 Collection method: not provided Allele origin: not provided Affected status: not provided

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
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

Text-mined citations for rs281875209 ...

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