Is GLA p.Gln279Glu (c.835C>G) pathogenic?

GLA p.Gln279Glu (c.835C>G) is classified Pathogenic/Likely pathogenic in GLA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-09-08). AlphaMissense: likely benign (0.1161); Very rare (popmax 0.00296%, eas); Associated with Fabry disease.

What condition is associated with GLA p.Gln279Glu (c.835C>G)?

GLA p.Gln279Glu (c.835C>G) is associated with Fabry disease (ClinVar).

How common is GLA p.Gln279Glu (c.835C>G) in the general population?

GLA p.Gln279Glu (c.835C>G) 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.Gln279Glu (c.835C>G)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

GLA p.Gln279Glu

c.835C>G · rs28935485 · VCV10721

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fabry disease

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign ⚠ discordant with ClinVar
REVEL	0.783	moderately pathogenic-leaning
SaProt	LLR -6.31	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 3.2, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 6,067 bp · p 6.6e-08 · regional, not allelic
Overall
CADD	25.0	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 · 1/33,840 alleles

Overall 8.28e-05% 1/1,208,331 alleles · very rare exomes 1/1,094,760 · genomes 0/113,571 · 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.Gln279Glu
Coding: c.835C>G
MANE Select: NM_000169
dbSNP: rs28935485
Type: single nucleotide variant
Location: chrX:101398534 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 279: a UniProt-annotated variant site (in fabryd; mild; does not significantly affect the enzyme activity but the mutant protein levels are decreased presumably in the er of the cells); a UniProt-annotated variant site (in fabryd); an α-helix

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.Gln279Arg Pathogenic ★★ same residue
GLA p.Gln279Ter Pathogenic ★★ same residue
GLA p.Gln279Leu Uncertain significance ★★ ⚠ same residue
GLA p.Gln279His Pathogenic ★ same residue
GLA p.Gln279Lys Pathogenic ★ same residue
GLA p.Gln279fs 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-gln279glu (accessed [today's date]).

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