Is GLA p.Arg332Glu (c.994_995delinsGA) pathogenic?

GLA p.Arg332Glu (c.994995delinsGA) is classified Uncertain significance in GLA (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-02-25). No gnomAD frequency available for this variant; Associated with Fabry disease.

What condition is associated with GLA p.Arg332Glu (c.994_995delinsGA)?

GLA p.Arg332Glu (c.994_995delinsGA) is associated with Fabry disease (ClinVar).

How common is GLA p.Arg332Glu (c.994_995delinsGA) in the general population?

GLA p.Arg332Glu (c.994_995delinsGA) is no gnomAD frequency available for this variant (gnomAD).

How is Fabry disease inherited?

Typically X-linked dominant, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GLA p.Arg332Glu

c.994_995delinsGA · rs1057518537 · VCV373666

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Fabry disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 2.5, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 6,067 bp · p 6.6e-08 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GLA
Protein: p.Arg332Glu
Coding: c.994_995delinsGA
MANE Select: NM_000169
dbSNP: rs1057518537
Type: Indel
Location: chrX:101398374 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 332: a β-strand

Full GLA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fabry disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fabry disease (Orphanet):

Inheritance: X-linked dominant, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

GLA p.Arg332fs Pathogenic ★ same residue
GLA p.Ala368fs Pathogenic ★★ same condition
GLA p.Asp55_Gln57delinsValCysLeu Pathogenic/Likely pathogenic ★★ same condition
GLA c.195-13_195-12delinsGC Uncertain significance ★★ same condition
GLA c.802-3_804delinsGGCAACTTT Likely pathogenic ★ same condition
GLA p.Ala73fs Pathogenic ★ same condition
GLA p.Arg356fs Likely pathogenic ★ same condition
GLA p.Asp231Tyr Likely pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gla-p-arg332glu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown