GPC3 p.Leu83=
c.249A>C · VCV3664416
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00176%, afr)
Conditions
1
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 -0.43 | GERP -4.7, phastCons 0.16 |
| Overall | ||
| CADD | 5.464 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00176%
African / African-American · 1/56,863 alleles
Overall
0.000899%
1/111,206 alleles · very rare
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.Leu83=
- Coding
- c.249A>C
- MANE Select
- NM_004484
- Type
- single nucleotide variant
- Location
- chrX:133953138 (GRCh38)
- Structure
- AlphaFold pLDDT 75.60 · 4 PDB
- Residue 83
- a disulfide bond; an α-helix
Similar variants
- GPC3 p.Leu83Arg 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-leu83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown