Is GPC3 p.Arg431= (c.1293A>G) pathogenic?

GPC3 p.Arg431= (c.1293A>G) is classified Conflicting classifications of pathogenicity in GPC3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-19). Absent from gnomAD v4.1; Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Arg431= (c.1293A>G)?

GPC3 p.Arg431= (c.1293A>G) is associated with Wilms tumor 1 (ClinVar).

How common is GPC3 p.Arg431= (c.1293A>G) in the general population?

GPC3 p.Arg431= (c.1293A>G) is absent from gnomAD v4.1 (gnomAD).

GPC3 p.Arg431=

c.1293A>G · rs2124401911 · VCV2994303

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Wilms tumor 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -1.2, phastCons 1
Overall
CADD	10.86	PHRED · no single calibrated threshold — expert panels disagree

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: GPC3
Protein: p.Arg431=
Coding: c.1293A>G
MANE Select: NM_004484
dbSNP: rs2124401911
Type: single nucleotide variant
Location: chrX:133661850 (GRCh38)
Structure: AlphaFold pLDDT 75.60 · 4 PDB
Residue 431: a β-strand

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 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
GPC3 c.1292+6C>T Uncertain significance ★★ same condition
GPC3 p.Ala141Thr Uncertain significance ★★ ⚠ 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-arg431 (accessed [today's date]).

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