Is GLA p.Tyr152Asp (c.454T>G) pathogenic?

GLA p.Tyr152Asp (c.454T>G) is classified Likely pathogenic in GLA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-09). AlphaMissense: ambiguous (0.5019); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Tyr152Asp (c.454T>G)?

GLA p.Tyr152Asp (c.454T>G) is associated with Cardiovascular phenotype, Fabry disease (ClinVar).

How common is GLA p.Tyr152Asp (c.454T>G) in the general population?

GLA p.Tyr152Asp (c.454T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLA p.Tyr152Asp (c.454T>G)?

AlphaMissense predicts ambiguous (score 0.5019) — an in-silico prediction, not a clinical call.

GLA p.Tyr152Asp

c.454T>G · rs1928323615 · VCV1038401

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5019 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.5019	ambiguous
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -15.09	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2.3, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 6,067 bp · p 6.6e-08 · regional, not allelic
Overall
CADD	25.7	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.Tyr152Asp
Coding: c.454T>G
MANE Select: NM_000169
dbSNP: rs1928323615
Type: single nucleotide variant
Location: chrX:101401725 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 152: an α-helix

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.Tyr152Ter Pathogenic ★★ same residue
GLA p.Tyr152Phe Uncertain significance ★★ ⚠ same residue
GLA p.Tyr152= Likely benign ★★ same residue
GLA p.Tyr152Cys Likely pathogenic ★ ⚠ same residue
GLA p.Tyr152His Likely pathogenic ★ ⚠ same residue
GLA p.Tyr152Ser Likely pathogenic ★ same residue
GLA p.Tyr152_Asp153insTyr Uncertain significance ★ same residue
GLA p.Tyr152del Conflicting classifications of pathogenicity ★ same residue

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-tyr152asp (accessed [today's date]).

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