Is GLA p.Glu203= (c.609G>A) pathogenic?

GLA p.Glu203= (c.609G>A) is classified Conflicting classifications of pathogenicity in GLA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-09-08). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Glu203= (c.609G>A)?

GLA p.Glu203= (c.609G>A) is associated with Cardiovascular phenotype, Fabry disease (ClinVar).

How common is GLA p.Glu203= (c.609G>A) in the general population?

GLA p.Glu203= (c.609G>A) is absent from gnomAD v4.1 (gnomAD).

GLA p.Glu203=

c.609G>A · VCV3520378

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,188,299)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.48	donor loss · deltas
Constraint at this position
Conservation	phyloP 1.1	GERP 2.8, phastCons 1
Overall
CADD	7.824	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,188,299). 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.Glu203=
Coding: c.609G>A
MANE Select: NM_000169
Type: single nucleotide variant
Location: chrX:101400696 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 203: a disulfide bond; a binding site

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

Disease context

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

Also linked: Fabry disease

Similar variants

GLA p.Glu203Ter Pathogenic ★ same residue
GLA p.Glu203Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
GLA p.Glu203Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
GLA p.Glu203Val Uncertain significance ★ ⚠ 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-glu203 (accessed [today's date]).

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