Is GPC3 p.Ile549= (c.1647A>T) pathogenic?

GPC3 p.Ile549= (c.1647A>T) is classified Likely benign in GPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-11). Absent from gnomAD v4.1; Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Ile549= (c.1647A>T)?

GPC3 p.Ile549= (c.1647A>T) is associated with Wilms tumor 1 (ClinVar).

How common is GPC3 p.Ile549= (c.1647A>T) in the general population?

GPC3 p.Ile549= (c.1647A>T) is absent from gnomAD v4.1 (gnomAD).

GPC3 p.Ile549=

c.1647A>T · rs2069289280 · VCV1086586

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -2.2	GERP -2.2
Overall
CADD	0.225	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GPC3
Protein: p.Ile549=
Coding: c.1647A>T
MANE Select: NM_004484
dbSNP: rs2069289280
Type: single nucleotide variant
Location: chrX:133536220 (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.Ile549Val 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
GPC3 p.Glu298Ter Pathogenic ★★ same condition
GPC3 c.1292+6C>T 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-ile549 (accessed [today's date]).

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