NM_000169.3(GLA):c.337_354del (p.Phe113_Arg118del) AND Fabry disease

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 15, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001537870.7

Allele description [Variation Report for NM_000169.3(GLA):c.337_354del (p.Phe113_Arg118del)]

NM_000169.3(GLA):c.337_354del (p.Phe113_Arg118del)

Genes:

RPL36A-HNRNPH2:RPL36A-HNRNPH2 readthrough [Gene - HGNC]
GLA:galactosidase alpha [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_000169.3(GLA):c.337_354del (p.Phe113_Arg118del)

HGVS:

NC_000023.11:g.101403829_101403846del
NG_007119.1:g.9121_9138del
NG_016327.1:g.627_644del
NM_000169.3:c.337_354delMANE SELECT
NM_001199973.2:c.301-8107_301-8090del
NM_001199974.2:c.178-8107_178-8090del
NM_001406747.1:c.460_477del
NM_001406748.1:c.337_354del
NM_001406749.1:c.460_477del
NP_000160.1:p.Phe113_Arg118del
NP_000160.1:p.Phe113_Arg118del
NP_001393676.1:p.Phe154_Arg159del
NP_001393677.1:p.Phe113_Arg118del
NP_001393678.1:p.Phe154_Arg159del
LRG_672t1:c.337_354del
LRG_672:g.9121_9138del
NC_000023.10:g.100658814_100658831del
NC_000023.10:g.100658817_100658834del
NM_000169.2:c.334_351del18
NM_000169.2:c.337_354del
NR_164783.1:n.359_376del
NR_176252.1:n.359_376del
NR_176253.1:n.359_376del

Links:

dbSNP: rs2147480442

Molecular consequence:

NM_000169.3:c.337_354del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406747.1:c.460_477del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406748.1:c.337_354del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406749.1:c.460_477del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001199973.2:c.301-8107_301-8090del - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.178-8107_178-8090del - intron variant - [Sequence Ontology: SO:0001627]
NR_164783.1:n.359_376del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176252.1:n.359_376del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.359_376del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Fabry disease
Synonyms:: ALPHA-GALACTOSIDASE A DEFICIENCY; ANDERSON-FABRY DISEASE; CERAMIDE TRIHEXOSIDASE DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010526; MedGen: C0002986; Orphanet: 324; OMIM: 301500; Human Phenotype Ontology: HP:0001071

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001754804	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004299647	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 25, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16773563, 17555407, 32099817, 7531540, 28492532
SCV006335463	Genomenon, Inc, Genomenon, Inc	criteria provided, single submitter (Genomenon Sequence Variant Interpretation Standards)	Pathogenic (Sep 15, 2025)	germline	curation	PubMed (4) [See all records that cite these PMIDs] 10649504, 27657681, 34363016, 7531540 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001754804

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 7, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004299647

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 25, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV006335463

Genomenon, Inc, Genomenon, Inc

criteria provided, single submitter

(Genomenon Sequence Variant Interpretation Standards)

Pathogenic
(Sep 15, 2025)

germline

curation

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

High incidence of later-onset fabry disease revealed by newborn screening.

Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan G, Sakuraba H, Ponzone A, Desnick RJ.

Am J Hum Genet. 2006 Jul;79(1):31-40. Epub 2006 Apr 28.

PubMed [citation]

PMID:: 16773563
PMCID:: PMC1474133

See all PubMed Citations (9)

Details of each submission

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV001754804.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The c.337_354del (p.Phe113_Arg118del) variant in the GLA gene is an in-frame deletion of 18 bp that is predicted to shorten the encoded protein by 6 amino acids but does not introduce a frameshift. Also known as c.333del18, this variant is a known pathogenic variant associated with the classic Fabry phenotype (PMID: 7531540). It is absent from general population databases. We consider this variant is to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004299647.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GLA protein in which other variant(s) (p.Phe113Leu) have been determined to be pathogenic (PMID: 16773563, 17555407, 32099817). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1180491). This variant has been observed in individuals with Fabry disease (PMID: 7531540; Invitae). This variant is not present in population databases (gnomAD no frequency). This variant, c.337_354del, results in the deletion of 6 amino acid(s) of the GLA protein (p.Phe113_Arg118del), but otherwise preserves the integrity of the reading frame.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genomenon, Inc, Genomenon, Inc, SCV006335463.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (4)

Description

GLA c.337_354del is an in-frame deletion variant that results in the deletion of multiple amino acids, from Phenylalanine at position 113 to Arginine at position 118. This variant has been observed in at least one proband affected with Fabry disease (PMID:7531540;10649504;34363016). At least one functional study has demonstrated a substantial alteration in protein function relative to the wild-type (PMID:27657681). It is absent or not present at a significant frequency in gnomAD. In conclusion, we classify GLA p.Phe113_Arg118del (c.337_354del) as a pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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