Is GPC3 p.Ser17fs (c.49del) pathogenic?

GPC3 p.Ser17fs (c.49del) is classified Pathogenic in GPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). Absent from gnomAD; Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Ser17fs (c.49del)?

GPC3 p.Ser17fs (c.49del) is associated with Wilms tumor 1 (ClinVar).

How common is GPC3 p.Ser17fs (c.49del) in the general population?

GPC3 p.Ser17fs (c.49del) is absent from gnomAD (gnomAD).

GPC3 p.Ser17fs

c.49del · rs2521972014 · VCV2742815

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 3.1	GERP -0.3, phastCons 1

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.Ser17fs
Coding: c.49del
MANE Select: NM_004484
dbSNP: rs2521972014
Type: Deletion
Location: chrX:133985401 (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.Ser17Cys Uncertain significance ★ ⚠ same residue
GPC3 p.Gln91fs Pathogenic/Likely pathogenic ★★ same condition
GPC3 c.338-5del Benign/Likely benign ★★ same condition
GPC3 c.338-7_338-5del Benign/Likely benign ★★ same condition
GPC3 c.1574-?_*379+?del Pathogenic ★ same condition
GPC3 p.Ala13fs Pathogenic ★ same condition
GPC3 p.Ala436fs Pathogenic ★ same condition
GPC3 p.Ala524fs 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-ser17fs (accessed [today's date]).

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