Is GPC3 p.Phe577del (c.1723TTC[2]) pathogenic?

GPC3 p.Phe577del (c.1723TTC[2]) is classified Uncertain significance in GPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). Very rare (popmax 0.000338%, nfe); Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Phe577del (c.1723TTC[2])?

GPC3 p.Phe577del (c.1723TTC[2]) is associated with Wilms tumor 1 (ClinVar).

How common is GPC3 p.Phe577del (c.1723TTC[2]) in the general population?

GPC3 p.Phe577del (c.1723TTC[2]) is very rare (popmax 0.000338%, nfe) (gnomAD).

GPC3 p.Phe577del

c.1723TTC[2] · rs1269354535 · VCV1017218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000338%, nfe)

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 · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP -0.02, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000338% European (non-Finnish) · 3/888,531 alleles

Filtering AF 9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.00025% 3/1,198,809 alleles · very rare exomes 3/1,092,182 · genomes 0/106,627 · 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.Phe577del
Coding: c.1723TTC[2]
MANE Select: NM_004484
dbSNP: rs1269354535
Type: Microsatellite
Location: chrX:133536136 (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.Phe577Leu Uncertain significance ★ ⚠ same residue
GPC3 p.Phe577= Likely benign ★ same residue
GPC3 p.Gln354del Uncertain significance ★★ same condition
GPC3 c.1574-7_1574-4del Benign/Likely benign ★★ same condition
GPC3 p.Ser460fs Pathogenic ★ same condition
GPC3 p.Tyr155fs Pathogenic ★ same condition
GPC3 p.Arg389del Uncertain significance ★ same condition
GPC3 p.Asp534del 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-phe577del (accessed [today's date]).

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