VCV001070568.9 - ClinVar

NM_000169.3(GLA):c.437del (p.Pro146fs)

Germline

Classification

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

Pathogenic

This classification is based on the single submission received

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_000169.3(GLA):c.437del (p.Pro146fs)

Variation ID: 1070568 Accession: VCV001070568.9

Type and length

Deletion, 1 bp

Location

Cytogenetic: Xq22.1 X: 101401742 (GRCh38) [ NCBI UCSC ] X: 100656730 (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	May 10, 2021	Feb 15, 2026	Jul 24, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_000169.3:c.437del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000160.1:p.Pro146fs	frameshift
NM_001199973.2:c.300+6287del		intron variant
NM_001199974.2:c.177+9922del		intron variant
NM_001406747.1:c.560del	NP_001393676.1:p.Pro187fs	frameshift
NM_001406748.1:c.437del	NP_001393677.1:p.Pro146fs	frameshift
NM_001406749.1:c.560del	NP_001393678.1:p.Pro187fs	frameshift
NR_164783.1:n.459del		non-coding transcript variant
NR_176252.1:n.459del		non-coding transcript variant
NR_176253.1:n.459del		non-coding transcript variant
NC_000023.11:g.101401744del
NC_000023.10:g.100656732del
NG_007119.1:g.11222del
LRG_672:g.11222del
LRG_672t1:c.435del	LRG_672p1:p.Pro146Leufs

... more HGVS ... less HGVS

Protein change

P146fs, P187fs

Other names

Canonical SPDI

NC_000023.11:101401741:GGG:GG

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: CA2499226277 dbSNP: rs2147477659 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.
GLA		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	6	2226
RPL36A-HNRNPH2	-	-	-	GRCh38 GRCh37	-	2305

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.
Fabry disease	Pathogenic (1)	criteria provided, single submitter	Jul 24, 2020	RCV001382760.10

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 (Jul 24, 2020) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Fabry disease	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001581664.6 First in ClinVar: May 10, 2021 Last updated: Feb 15, 2026	Publications: PubMed (2) PubMed: 10666480‚ 12175777 Comment: show This sequence change creates a premature translational stop signal (p.Pro146Leufs*19) in the GLA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Fabry disease (Invitae). Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). 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

Comment:

This sequence change creates a premature translational stop signal (p.Pro146Leufs*19) in the GLA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Fabry disease (Invitae). Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Fabry disease: 45 novel mutations in the alpha-galactosidase A gene causing the classical phenotype.	Shabbeer J	Molecular genetics and metabolism	2002	PMID: 12175777
Twenty novel mutations in the alpha-galactosidase A gene causing Fabry disease.	Topaloglu AK	Molecular medicine (Cambridge, Mass.)	1999	PMID: 10666480

Text-mined citations for rs2147477659 ...

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