Is GLA p.Asp83Asn (c.247G>A) pathogenic?

GLA p.Asp83Asn (c.247G>A) is classified Conflicting classifications of pathogenicity in GLA (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-09-08). AlphaMissense: likely benign (0.0813); Very rare (popmax 0.00493%, nfe); Associated with Charcot-Marie-Tooth disease.

What condition is associated with GLA p.Asp83Asn (c.247G>A)?

GLA p.Asp83Asn (c.247G>A) is associated with Charcot-Marie-Tooth disease, Fabry disease (ClinVar).

How common is GLA p.Asp83Asn (c.247G>A) in the general population?

GLA p.Asp83Asn (c.247G>A) is very rare (popmax 0.00493%, nfe) (gnomAD).

What do computational predictors say about GLA p.Asp83Asn (c.247G>A)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

GLA p.Asp83Asn

c.247G>A · rs782722577 · VCV222202

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00493%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.644	pathogenic-leaning
SaProt	LLR -11.59	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 3.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 3,899 bp · p 4.8e-07 · regional, not allelic
Overall
CADD	23.4	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 0.00493% European (non-Finnish) · 44/892,426 alleles

Filtering AF 0.00374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00333%

Overall 0.00373% 45/1,207,559 alleles · very rare exomes 44/1,094,910 · genomes 1/112,649 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00493%	20,282
African / African-American	0.00174%	57,372

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.Asp83Asn
Coding: c.247G>A
MANE Select: NM_000169
dbSNP: rs782722577
Type: single nucleotide variant
Location: chrX:101403933 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 83: an α-helix

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

Disease context

Charcot-Marie-Tooth disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fabry disease

Similar variants

GLA p.Asp83= Likely benign ★★ 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
GLA c.194+1G>A Pathogenic ★★ same condition
GLA c.194+1G>T Pathogenic ★★ same condition
GLA c.195-1G>C 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-asp83asn (accessed [today's date]).

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