Is GLA p.Tyr152= (c.456C>T) pathogenic?

GLA p.Tyr152= (c.456C>T) is classified Likely benign in GLA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-09-08). Very rare (popmax 0.000561%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Tyr152= (c.456C>T)?

GLA p.Tyr152= (c.456C>T) is associated with Cardiovascular phenotype, Fabry disease (ClinVar).

How common is GLA p.Tyr152= (c.456C>T) in the general population?

GLA p.Tyr152= (c.456C>T) is very rare (popmax 0.000561%, nfe) (gnomAD).

GLA p.Tyr152=

c.456C>T · rs1555985827 · VCV1097822

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000561%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP 1.1, phastCons 0.92
Overall
CADD	4.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000561% European (non-Finnish) · 5/891,567 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000414% 5/1,207,392 alleles · very rare exomes 5/1,093,816 · genomes 0/113,576 · joint denominator

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.Tyr152=
Coding: c.456C>T
MANE Select: NM_000169
dbSNP: rs1555985827
Type: single nucleotide variant
Location: chrX:101401723 (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.Tyr152Asp Likely pathogenic ★★ same residue
GLA p.Tyr152Ter Pathogenic ★★ same residue
GLA p.Tyr152Phe Uncertain significance ★★ ⚠ 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-tyr152 (accessed [today's date]).

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