Is GLA p.Leu32Pro (c.95T>C) pathogenic?

GLA p.Leu32Pro (c.95T>C) is classified Pathogenic/Likely pathogenic in GLA (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-09-08). AlphaMissense: ambiguous (0.4887); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Leu32Pro (c.95T>C)?

GLA p.Leu32Pro (c.95T>C) is associated with Cardiovascular phenotype, Fabry disease (ClinVar).

How common is GLA p.Leu32Pro (c.95T>C) in the general population?

GLA p.Leu32Pro (c.95T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLA p.Leu32Pro (c.95T>C)?

AlphaMissense predicts ambiguous (score 0.4887) — an in-silico prediction, not a clinical call.

GLA p.Leu32Pro

c.95T>C · rs1569306168 · VCV592219

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.4887 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4887	ambiguous
REVEL	0.961	strongly pathogenic-leaning
SaProt	LLR -8.75	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 3.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 123 bp · p 0.7 · regional, not allelic
Overall
CADD	25.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GLA
Protein: p.Leu32Pro
Coding: c.95T>C
MANE Select: NM_000169
dbSNP: rs1569306168
Type: single nucleotide variant
Location: chrX:101407809 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 32: a UniProt-annotated variant site (in fabryd)

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

Similar variants

GLA p.Leu32Gln 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
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-leu32pro (accessed [today's date]).

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