Is GLA p.Cys202Ser (c.605G>C) pathogenic?

GLA p.Cys202Ser (c.605G>C) is classified Likely pathogenic in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-27). AlphaMissense: likely pathogenic (0.9606); Very rare (popmax 0.00296%, eas); Associated with Fabry disease.

What condition is associated with GLA p.Cys202Ser (c.605G>C)?

GLA p.Cys202Ser (c.605G>C) is associated with Fabry disease (ClinVar).

How common is GLA p.Cys202Ser (c.605G>C) in the general population?

GLA p.Cys202Ser (c.605G>C) is very rare (popmax 0.00296%, eas) (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 p.Cys202Ser (c.605G>C)?

AlphaMissense predicts likely pathogenic (score 0.9606) — an in-silico prediction, not a clinical call.

GLA p.Cys202Ser

c.605G>C · rs869312344 · VCV1466492

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fabry disease

Computational evidence

Protein change
AlphaMissense	0.9606	likely pathogenic ✓ concordant with ClinVar · top 3% in GLA
REVEL	0.972	strongly pathogenic-leaning
SaProt	LLR -9.73	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.48	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 6,067 bp · p 6.6e-08 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.00296% East Asian · 1/33,777 alleles

Overall 9.28e-05% 1/1,077,491 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GLA
Protein: p.Cys202Ser
Coding: c.605G>C
MANE Select: NM_000169
dbSNP: rs869312344
Type: single nucleotide variant
Location: chrX:101400700 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 202: a disulfide bond; a UniProt-annotated variant site (in fabryd); a UniProt-annotated variant site (in fabryd; loss of enzyme activity); 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.Cys202Arg Pathogenic/Likely pathogenic ★★ same residue
GLA p.Cys202Trp Pathogenic ★★ same residue
GLA p.Cys202Tyr Pathogenic/Likely pathogenic ★★ same residue
GLA p.Cys202Phe Uncertain significance ★ ⚠ same residue
GLA p.Cys202_Glu203delinsTer Pathogenic ★ same residue
GLA p.Cys202fs Pathogenic ★ same residue
GLA c.1000-10G>A Likely pathogenic ★★ same condition
GLA c.1000-1G>A 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-cys202ser (accessed [today's date]).

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