Is GPC3 p.Thr7= (c.21C>T) pathogenic?

GPC3 p.Thr7= (c.21C>T) is classified Likely benign in GPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). Very rare (popmax 0.0025%, amr); Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Thr7= (c.21C>T)?

GPC3 p.Thr7= (c.21C>T) is associated with Wilms tumor 1 (ClinVar).

How common is GPC3 p.Thr7= (c.21C>T) in the general population?

GPC3 p.Thr7= (c.21C>T) is very rare (popmax 0.0025%, amr) (gnomAD).

GPC3 p.Thr7=

c.21C>T · rs192833218 · VCV1155285

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0025%, amr)

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 9.7	GERP 1.7, phastCons 1
Overall
CADD	15.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0025% Admixed American · 1/40,079 alleles

Filtering AF 0.000167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000511% 6/1,173,708 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0025%	40,079
European (non-Finnish)	0.00057%	175,401

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.Thr7=
Coding: c.21C>T
MANE Select: NM_004484
dbSNP: rs192833218
Type: single nucleotide variant
Location: chrX:133985429 (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.Thr7Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
GPC3 p.Thr7Ser 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

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-thr7 (accessed [today's date]).

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