PAK3 p.Pro414=
c.1242T>C · rs2524222965 · VCV2661201
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000112%, nfe)
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 -0.73 | GERP -3.6, phastCons 0.016 |
| Overall | ||
| CADD | 9.257 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000112%
European (non-Finnish) · 1/894,447 alleles
Overall
8.26e-05%
1/1,210,881 alleles · very rare
exomes 1/1,096,944 · genomes 0/113,937 · 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.Pro414=
- Coding
- c.1242T>C
- MANE Select
- NM_002578
- dbSNP
- rs2524222965
- Type
- single nucleotide variant
- Location
- chrX:111196475 (GRCh38)
- Structure
- AlphaFold pLDDT 66.31 · 4 PDB
- Residue 414
- the dh domain
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-pro414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown