Is GLA p.Asp231Ala (c.692A>C) pathogenic?

GLA p.Asp231Ala (c.692A>C) is classified Conflicting classifications of pathogenicity in GLA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2021-07-15). AlphaMissense: likely pathogenic (0.8784); Absent from gnomAD v4.1; Associated with GLA-related disorder.

What condition is associated with GLA p.Asp231Ala (c.692A>C)?

GLA p.Asp231Ala (c.692A>C) is associated with GLA-related disorder, Fabry disease (ClinVar).

How common is GLA p.Asp231Ala (c.692A>C) in the general population?

GLA p.Asp231Ala (c.692A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLA p.Asp231Ala (c.692A>C)?

AlphaMissense predicts likely pathogenic (score 0.8784) — an in-silico prediction, not a clinical call.

GLA p.Asp231Ala

c.692A>C · rs1569303295 · VCV578114

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8784 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GLA-related disorder

Computational evidence

Protein change
AlphaMissense	0.8784	likely pathogenic
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -14.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 3.2, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 6,067 bp · p 6.6e-08 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GLA
Protein: p.Asp231Ala
Coding: c.692A>C
MANE Select: NM_000169
dbSNP: rs1569303295
Type: single nucleotide variant
Location: chrX:101398894 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 231: a UniProt-annotated variant site (in fabryd); an α-helix; an active site

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

Disease context

GLA-related disorder

Also linked: Fabry disease

Similar variants

GLA p.Asp231Gly Pathogenic/Likely pathogenic ★★ same residue
GLA p.Asp231Asn Pathogenic ★ same residue
GLA p.Asp231Val Pathogenic ★ same residue
GLA p.Asp231Tyr Likely pathogenic ★ same residue
GLA c.1000-10G>A Likely pathogenic ★★ same condition
GLA c.1000-1G>A Pathogenic ★★ same condition
GLA c.1000-1G>C Pathogenic ★★ same condition
GLA c.1023A>C Pathogenic/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-asp231ala (accessed [today's date]).

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