Is GLA p.Ala15Val (c.44C>T) pathogenic?

GLA p.Ala15Val (c.44C>T) is classified Uncertain significance in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). AlphaMissense: likely benign (0.0846); Very rare (popmax 0.00698%, afr); Associated with Fabry disease.

What condition is associated with GLA p.Ala15Val (c.44C>T)?

GLA p.Ala15Val (c.44C>T) is associated with Fabry disease (ClinVar).

How common is GLA p.Ala15Val (c.44C>T) in the general population?

GLA p.Ala15Val (c.44C>T) is very rare (popmax 0.00698%, afr) (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.Ala15Val (c.44C>T)?

AlphaMissense predicts likely benign (score 0.0846) — an in-silico prediction, not a clinical call.

GLA p.Ala15Val

c.44C>T · rs869312304 · VCV3075068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0846 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00698%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fabry disease

Computational evidence

Protein change
AlphaMissense	0.0846	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -5.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -0.81
Regional constraint	o/e 0.93	unconstrained · MANE · 123 bp · p 0.7 · regional, not allelic
Overall
CADD	6.852	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00698% African / African-American · 4/57,270 alleles

Filtering AF 0.00233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.000331% 4/1,209,976 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.Ala15Val
Coding: c.44C>T
MANE Select: NM_000169
dbSNP: rs869312304
Type: single nucleotide variant
Location: chrX:101407860 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB

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.Ala15Glu Pathogenic ★★ ⚠ same residue
GLA p.Ala15Thr Uncertain significance ★★ ⚠ same residue
GLA p.Ala15Gly Likely pathogenic ★ ⚠ same residue
GLA p.Ala15Pro Likely pathogenic ★ ⚠ 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-ala15val (accessed [today's date]).

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