PAK3 p.Val259=
c.777G>C · rs757757597 · VCV726484
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.022%, amr)
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 0.75 | GERP 0.99, phastCons 1 |
| Overall | ||
| CADD | 5.277 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.022%
Admixed American · 10/45,535 alleles
Filtering AF
0.0119%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00905%
Overall
0.000886%
10/1,128,632 alleles · ultra-rare
exomes 10/1,016,220 · genomes 0/112,412 · 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
- PAK3
- Protein
- p.Val259=
- Coding
- c.777G>C
- MANE Select
- NM_002578
- dbSNP
- rs757757597
- Type
- single nucleotide variant
- Location
- chrX:111173028 (GRCh38)
- Structure
- AlphaFold pLDDT 66.31 · 4 PDB
Similar variants
- PAK3 p.Arg100Ter Pathogenic/Likely pathogenic ★★ same type
- PAK3 p.Arg436Ter Pathogenic/Likely pathogenic ★★ same type
- PAK3 p.Glu356Ter Pathogenic/Likely pathogenic ★★ same type
- PAK3 c.830+6T>A Uncertain significance ★★ same type
- PAK3 p.Ala490Thr Uncertain significance ★★ ⚠ same type
- PAK3 p.Arg493Cys Uncertain significance ★★ ⚠ same type
- PAK3 p.Arg498Cys Uncertain significance ★★ ⚠ same type
- PAK3 p.Asn185Thr 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/pak3-p-val259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown