Is GPC3 p.Ser460fs (c.1379_1382del) pathogenic?

GPC3 p.Ser460fs (c.13791382del) is classified Pathogenic in GPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-15). No gnomAD frequency available for this variant; Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Ser460fs (c.1379_1382del)?

GPC3 p.Ser460fs (c.1379_1382del) is associated with Wilms tumor 1 (ClinVar).

How common is GPC3 p.Ser460fs (c.1379_1382del) in the general population?

GPC3 p.Ser460fs (c.1379_1382del) is no gnomAD frequency available for this variant (gnomAD).

GPC3 p.Ser460fs

c.1379_1382del · rs2124401794 · VCV1453391

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 6 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.055	GERP 0.037, phastCons 0.96

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.Ser460fs
Coding: c.1379_1382del
MANE Select: NM_004484
dbSNP: rs2124401794
Type: Microsatellite
Location: chrX:133661761 (GRCh38)
Structure: AlphaFold pLDDT 75.60 · 4 PDB
Residue 460: 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.Ser460Arg Uncertain significance ★ ⚠ same residue
GPC3 p.Gln354del Uncertain significance ★★ same condition
GPC3 c.1574-7_1574-4del Benign/Likely benign ★★ same condition
GPC3 p.Tyr155fs Pathogenic ★ same condition
GPC3 p.Arg389del Uncertain significance ★ same condition
GPC3 p.Asp534del Uncertain significance ★ same condition
GPC3 p.Phe577del Uncertain significance ★ same condition
GPC3 p.Pro30_Pro31del 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-ser460fs (accessed [today's date]).

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