Is GPC3 p.Pro28fs (c.80dup) pathogenic?

GPC3 p.Pro28fs (c.80dup) is classified Pathogenic in GPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-08). No gnomAD frequency available for this variant; Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Pro28fs (c.80dup)?

GPC3 p.Pro28fs (c.80dup) is associated with Wilms tumor 1 (ClinVar).

How common is GPC3 p.Pro28fs (c.80dup) in the general population?

GPC3 p.Pro28fs (c.80dup) is no gnomAD frequency available for this variant (gnomAD).

GPC3 p.Pro28fs

c.80dup · rs1602581162 · VCV656012

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Wilms tumor 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -1.3, phastCons 1
Region caveats
Repeat context	tandem	(GGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GPC3
Protein: p.Pro28fs
Coding: c.80dup
MANE Select: NM_004484
dbSNP: rs1602581162
Type: Duplication
Location: chrX:133985369 (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.Pro28Leu Uncertain significance ★ ⚠ same residue
GPC3 c.338-20dup Benign/Likely benign ★★ same condition
GPC3 c.338-6_338-5dup Likely benign ★★ same condition
GPC3 p.Asp172Ter Pathogenic ★ same condition
GPC3 p.Gly48fs Pathogenic ★ same condition
GPC3 c.-197-?_*379+?dup Uncertain significance ★ same condition
GPC3 p.Pro29_Pro31dup Uncertain significance ★ same condition
GPC3 c.1033-9dup Likely benign ★ 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-pro28fs (accessed [today's date]).

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