Is GLA c.1023A>C pathogenic?

GLA c.1023A>C is classified Pathogenic/Likely pathogenic in GLA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-09-08). AlphaMissense: likely pathogenic (0.8283); Absent from gnomAD v4.1; Associated with Fabry disease.

What condition is associated with GLA c.1023A>C?

GLA c.1023A>C is associated with Fabry disease (ClinVar).

How common is GLA c.1023A>C in the general population?

GLA c.1023A>C is absent from gnomAD v4.1 (gnomAD).

How is Fabry disease inherited?

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

What do computational predictors say about GLA c.1023A>C?

AlphaMissense predicts likely pathogenic (score 0.8283) — an in-silico prediction, not a clinical call.

GLA c.1023A>C

rs797044497 · VCV167136

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8283 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fabry disease

Computational evidence

Protein change
AlphaMissense	0.8283	likely pathogenic ✓ concordant with ClinVar
REVEL	0.696	pathogenic-leaning
SaProt	LLR -7.74	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.65	GERP -2.1, phastCons 1
Non-coding constraint	—	not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained
Overall
CADD	18.67	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
Coding: c.1023A>C
MANE Select: NM_000169
dbSNP: rs797044497
Type: single nucleotide variant
Location: chrX:101398076 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB

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 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.194+1G>A Pathogenic ★★ same condition
GLA c.194+1G>T Pathogenic ★★ same condition
GLA c.195-1G>C Pathogenic ★★ same condition
GLA c.195-1G>T Pathogenic ★★ same condition
GLA c.195-2A>G 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-c-1023a-c (accessed [today's date]).

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