Is GPC3 p.Pro30= (c.90G>A) pathogenic?

GPC3 p.Pro30= (c.90G>A) is classified Likely benign in GPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-03). Very rare (popmax 0.0018%, sas); Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Pro30= (c.90G>A)?

GPC3 p.Pro30= (c.90G>A) is associated with Wilms tumor 1 (ClinVar).

How common is GPC3 p.Pro30= (c.90G>A) in the general population?

GPC3 p.Pro30= (c.90G>A) is very rare (popmax 0.0018%, sas) (gnomAD).

GPC3 p.Pro30=

c.90G>A · rs2124655746 · VCV1090609

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0018%, sas)

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 -0.035	GERP -2.6, phastCons 0.42
Overall
CADD	11.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0018% South Asian · 1/55,483 alleles

Overall 8.32e-05% 1/1,202,022 alleles · very rare exomes 1/1,089,043 · genomes 0/112,979 · 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: GPC3
Protein: p.Pro30=
Coding: c.90G>A
MANE Select: NM_004484
dbSNP: rs2124655746
Type: single nucleotide variant
Location: chrX:133985360 (GRCh38)
Structure: AlphaFold pLDDT 75.60 · 4 PDB

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.Pro30Ser Uncertain significance ★ ⚠ same residue
GPC3 p.Pro30_Pro31del Uncertain significance ★ same residue
GPC3 p.Pro30_Pro31insThr 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

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-pro30 (accessed [today's date]).

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