Is GPC3 p.Asp172= (c.516C>T) pathogenic?

GPC3 p.Asp172= (c.516C>T) is classified Likely benign in GPC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0298%, afr); Associated with Wilms tumor 1.

What condition is associated with GPC3 p.Asp172= (c.516C>T)?

GPC3 p.Asp172= (c.516C>T) is associated with Wilms tumor 1, Simpson-Golabi-Behmel syndrome type 1 (ClinVar).

How common is GPC3 p.Asp172= (c.516C>T) in the general population?

GPC3 p.Asp172= (c.516C>T) is ultra-rare (popmax 0.0298%, afr) (gnomAD).

GPC3 p.Asp172=

c.516C>T · rs369607601 · VCV415277

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0298%, afr)

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 1.6	GERP -4.4, phastCons 1
Overall
CADD	5.097	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0298% African / African-American · 17/57,051 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0156%

Overall 0.00149% 18/1,209,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0298%	3,356
Finnishnot grpmax-eligible	0.00215%	46,563

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.Asp172=
Coding: c.516C>T
MANE Select: NM_004484
dbSNP: rs369607601
Type: single nucleotide variant
Location: chrX:133753998 (GRCh38)
Structure: AlphaFold pLDDT 75.60 · 4 PDB
Residue 172: an α-helix

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.Asp172Ter Pathogenic ★ 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 p.Gly556Arg Pathogenic/Likely 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-asp172 (accessed [today's date]).

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