Is GPC3 p.Ala128= (c.384C>T) pathogenic?

GPC3 p.Ala128= (c.384C>T) is classified Benign in GPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-17). Very rare (popmax 0.00672%, nfe); Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Ala128= (c.384C>T)?

GPC3 p.Ala128= (c.384C>T) is associated with Wilms tumor 1 (ClinVar).

How common is GPC3 p.Ala128= (c.384C>T) in the general population?

GPC3 p.Ala128= (c.384C>T) is very rare (popmax 0.00672%, nfe) (gnomAD).

GPC3 p.Ala128=

c.384C>T · rs761541528 · VCV543105

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00672%, nfe)

Conditions

Wilms tumor 1

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 5.9	GERP 0.29, phastCons 1
Overall
CADD	9.792	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00672% European (non-Finnish) · 60/892,509 alleles

Filtering AF 0.00531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00478%

Overall 0.00498% 60/1,204,923 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: GPC3
Protein: p.Ala128=
Coding: c.384C>T
MANE Select: NM_004484
dbSNP: rs761541528
Type: single nucleotide variant
Location: chrX:133754130 (GRCh38)
Structure: AlphaFold pLDDT 75.60 · 4 PDB
Residue 128: a disulfide bond; an α-helix

Full GPC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Wilms tumor 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GPC3 p.Ala128Asp Uncertain significance ★ ⚠ same residue
GPC3 p.Ala128Thr Uncertain significance ★ ⚠ same residue
GPC3 c.337+2T>A Likely pathogenic ★★ same condition
GPC3 p.Arg199Ter Pathogenic ★★ same condition
GPC3 p.Arg254Ter Pathogenic ★★ same condition
GPC3 p.Arg387Ter Pathogenic ★★ same condition
GPC3 p.Arg86Ter Pathogenic ★★ same condition
GPC3 p.Glu298Ter 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/gpc3-p-ala128 (accessed [today's date]).

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