Is GLA p.Glu87Ala (c.260A>C) pathogenic?

GLA p.Glu87Ala (c.260A>C) is classified Uncertain significance in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-20). AlphaMissense: likely benign (0.1494); Very rare (popmax 0.000112%, nfe).

How common is GLA p.Glu87Ala (c.260A>C) in the general population?

GLA p.Glu87Ala (c.260A>C) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about GLA p.Glu87Ala (c.260A>C)?

AlphaMissense predicts likely benign (score 0.1494) — an in-silico prediction, not a clinical call.

GLA p.Glu87Ala

c.260A>C · VCV4952051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1494 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1494	likely benign
REVEL	0.623	indeterminate
SaProt	LLR -12.87	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.85, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 3,899 bp · p 4.8e-07 · regional, not allelic
Overall
CADD	24.3	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) · 1/891,522 alleles

Overall 0.000887% 1/112,756 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.Glu87Ala
Coding: c.260A>C
MANE Select: NM_000169
Type: single nucleotide variant
Location: chrX:101403920 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 87: a disulfide bond

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

Similar variants

GLA p.Glu87Lys Uncertain significance ★★ ⚠ same residue
GLA p.Glu87Val Uncertain significance ★★ ⚠ same residue
GLA p.Glu87_Asp92del Pathogenic ★ same residue
GLA p.Glu87fs Pathogenic ★ same residue
GLA c.1000-10G>A Likely pathogenic ★★ same type
GLA c.1000-1G>A Pathogenic ★★ same type
GLA c.1000-1G>C Pathogenic ★★ same type
GLA c.1023A>C Pathogenic/Likely pathogenic ★★ ⚠ same type

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-glu87ala (accessed [today's date]).

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