Is GPC3 p.Asp500= (c.1500T>C) pathogenic?

GPC3 p.Asp500= (c.1500T>C) is classified Benign in GPC3 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Common (popmax 22.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Asp500= (c.1500T>C)?

GPC3 p.Asp500= (c.1500T>C) is associated with Wilms tumor 1, hereditary neoplastic syndrome, Simpson-Golabi-Behmel syndrome type 1 (ClinVar).

GPC3 p.Asp500=

Q: How common is GPC3 p.Asp500= (c.1500T>C) in the general population?

GPC3 p.Asp500= (c.1500T>C) is common (popmax 22.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1500T>C · rs2314298 · VCV259405

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 22.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Wilms tumor 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.254	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -3.7
Overall
CADD	0.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.1% African / African-American · 12,573/56,799 alleles

Filtering AF 21.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.7%

Overall 1.25% 15,052/1,203,953 alleles · common exomes 8,092/1,092,330 · genomes 6,960/111,623 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.1%	5
Remaining individualsnot grpmax-eligible	1.83%	55
Admixed American	1.6%	63
Middle Eastern	1.5%	67
Ashkenazi Jewishnot grpmax-eligible	0.677%	148
European (non-Finnish)	0.0717%	1,395
South Asian	0.0494%	2,023
Finnishnot grpmax-eligible	0.00215%	46,581

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.Asp500=
Coding: c.1500T>C
MANE Select: NM_004484
dbSNP: rs2314298
Type: single nucleotide variant
Location: chrX:133596513 (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: hereditary neoplastic syndrome Simpson-Golabi-Behmel syndrome type 1

Similar variants

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 p.Gly556Arg Pathogenic/Likely 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-asp500 (accessed [today's date]).

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