Is GLA p.Leu191Pro (c.572T>C) pathogenic?

GLA p.Leu191Pro (c.572T>C) is classified Pathogenic/Likely pathogenic in GLA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-09-08). AlphaMissense: likely pathogenic (0.9792); Absent from gnomAD v4.1; Associated with GLA-related disorder.

What condition is associated with GLA p.Leu191Pro (c.572T>C)?

GLA p.Leu191Pro (c.572T>C) is associated with GLA-related disorder, Fabry disease (ClinVar).

How common is GLA p.Leu191Pro (c.572T>C) in the general population?

GLA p.Leu191Pro (c.572T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLA p.Leu191Pro (c.572T>C)?

AlphaMissense predicts likely pathogenic (score 0.9792) — an in-silico prediction, not a clinical call.

GLA p.Leu191Pro

c.572T>C · rs111972736 · VCV4087422

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9792 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,170,175)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GLA-related disorder

Computational evidence

Protein change
AlphaMissense	0.9792	likely pathogenic ✓ concordant with ClinVar · top 1% in GLA
REVEL	0.741	pathogenic-leaning
SaProt	LLR -17.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 6,067 bp · p 6.6e-08 · regional, not allelic
Overall
CADD	28.9	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

No allele count reported in gnomAD v4.1 (AN 1,170,175). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GLA
Protein: p.Leu191Pro
Coding: c.572T>C
MANE Select: NM_000169
dbSNP: rs111972736
Type: single nucleotide variant
Location: chrX:101400733 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 191: an α-helix

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

Disease context

GLA-related disorder

Also linked: Fabry disease

Similar variants

GLA p.Leu191Gln Likely pathogenic ★ same residue
GLA p.Leu191= Likely benign ★ same residue
GLA p.Leu191fs 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

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-leu191pro (accessed [today's date]).

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