Is GLA p.Cys202Phe (c.605G>T) pathogenic?

GLA p.Cys202Phe (c.605G>T) is classified Uncertain significance in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-09-08). AlphaMissense: likely pathogenic (0.9608); Absent from gnomAD v4.1; Associated with Fabry disease.

What condition is associated with GLA p.Cys202Phe (c.605G>T)?

GLA p.Cys202Phe (c.605G>T) is associated with Fabry disease (ClinVar).

How common is GLA p.Cys202Phe (c.605G>T) in the general population?

GLA p.Cys202Phe (c.605G>T) 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 p.Cys202Phe (c.605G>T)?

AlphaMissense predicts likely pathogenic (score 0.9608) — an in-silico prediction, not a clinical call.

GLA p.Cys202Phe

c.605G>T · VCV4087428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9608 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,191,266)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fabry disease

Computational evidence

Protein change
AlphaMissense	0.9608	likely pathogenic · top 3% in GLA
REVEL	0.979	strongly pathogenic-leaning
SaProt	LLR -14.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	29.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,191,266). 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.Cys202Phe
Coding: c.605G>T
MANE Select: NM_000169
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.Cys202Ser Likely pathogenic ★ ⚠ 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-cys202phe (accessed [today's date]).

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