Is GLA p.Arg301Gln (c.902G>A) pathogenic?

GLA p.Arg301Gln (c.902G>A) is classified Pathogenic in GLA (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-09-08). AlphaMissense: likely benign (0.1501); Very rare (popmax 0.000112%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Arg301Gln (c.902G>A)?

GLA p.Arg301Gln (c.902G>A) is associated with Cardiovascular phenotype, Fabry disease, familial hypertrophic cardiomyopathy (ClinVar).

How common is GLA p.Arg301Gln (c.902G>A) in the general population?

GLA p.Arg301Gln (c.902G>A) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about GLA p.Arg301Gln (c.902G>A)?

AlphaMissense predicts likely benign (score 0.1501) — an in-silico prediction, not a clinical call.

GLA p.Arg301Gln

c.902G>A · rs104894828 · VCV10715

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.1501 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1501	likely benign ⚠ discordant with ClinVar
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -12.25	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 3.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 6,067 bp · p 6.6e-08 · regional, not allelic
Overall
CADD	27.2	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 0.000112% European (non-Finnish) · 1/890,079 alleles

Overall 8.3e-05% 1/1,205,499 alleles · very rare exomes 1/1,092,233 · genomes 0/113,266 · joint denominator

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.Arg301Gln
Coding: c.902G>A
MANE Select: NM_000169
dbSNP: rs104894828
Type: single nucleotide variant
Location: chrX:101398467 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 301: a UniProt-annotated variant site (in fabryd; does not significantly affect the enzyme activity but the mutant protein levels are decreased presumably in the er of the cells)

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 familial hypertrophic cardiomyopathy

Similar variants

GLA p.Arg301Gly Pathogenic ★★ same residue
GLA p.Arg301Pro Pathogenic ★★ same residue
GLA p.Arg301Ter Pathogenic ★★ same residue
GLA p.Arg301Leu Pathogenic ★ same residue
GLA p.Arg301= Likely benign ★ same residue
GLA p.Arg301fs 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-arg301gln (accessed [today's date]).

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