Is GPC3 p.Thr7Pro (c.19A>C) pathogenic?

GPC3 p.Thr7Pro (c.19A>C) is classified Conflicting classifications of pathogenicity in GPC3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-06). AlphaMissense: likely benign (0.0902); Absent from gnomAD v4.1; Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Thr7Pro (c.19A>C)?

GPC3 p.Thr7Pro (c.19A>C) is associated with Wilms tumor 1, Simpson-Golabi-Behmel syndrome type 1 (ClinVar).

How common is GPC3 p.Thr7Pro (c.19A>C) in the general population?

GPC3 p.Thr7Pro (c.19A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GPC3 p.Thr7Pro (c.19A>C)?

AlphaMissense predicts likely benign (score 0.0902) — an in-silico prediction, not a clinical call.

GPC3 p.Thr7Pro

c.19A>C · rs773144223 · VCV1014539

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0902 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Wilms tumor 1

Computational evidence

Protein change
AlphaMissense	0.0902	likely benign
REVEL	0.262	benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.54, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 449 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	19.24	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Thr7Pro
Coding: c.19A>C
MANE Select: NM_004484
dbSNP: rs773144223
Type: single nucleotide variant
Location: chrX:133985431 (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

Also linked: Simpson-Golabi-Behmel syndrome type 1

Similar variants

GPC3 p.Thr7Ser Uncertain significance ★ ⚠ same residue
GPC3 p.Thr7= Likely benign ★ 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

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-thr7pro (accessed [today's date]).

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