GPC3 p.Lys435=
c.1305G>A · rs893970724 · VCV757256
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00176%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.043 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 8.489 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00176%
African / African-American · 1/56,887 alleles
Overall
8.33e-05%
1/1,200,644 alleles · very rare
exomes 1/1,089,295 · genomes 0/111,349 · joint denominator
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.Lys435=
- Coding
- c.1305G>A
- MANE Select
- NM_004484
- dbSNP
- rs893970724
- Type
- single nucleotide variant
- Location
- chrX:133661838 (GRCh38)
- Structure
- AlphaFold pLDDT 75.60 · 4 PDB
Similar variants
- GPC3 c.337+2T>A Likely pathogenic ★★ same type
- GPC3 p.Arg199Ter Pathogenic ★★ same type
- GPC3 p.Arg254Ter Pathogenic ★★ same type
- GPC3 p.Arg387Ter Pathogenic ★★ same type
- GPC3 p.Arg86Ter Pathogenic ★★ same type
- GPC3 p.Glu298Ter Pathogenic ★★ same type
- GPC3 p.Gly556Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
- GPC3 c.1292+6C>T Uncertain significance ★★ same type
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-lys435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown