PAK3 p.Pro12=
c.36G>A · rs142774727 · VCV2049484
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0492%, afr)
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 0.91 | phastCons 0.98 |
| Overall | ||
| CADD | 7.737 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0492%
African / African-American · 28/56,929 alleles
Filtering AF
0.0349%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0301%
Overall
0.00365%
44/1,205,167 alleles · ultra-rare
exomes 24/1,093,831 · genomes 20/111,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0492% | 2,033 |
| Admixed American | 0.0131% | 7,618 |
| Remaining individualsnot grpmax-eligible | 0.00632% | 15,830 |
| South Asian | 0.00177% | 56,642 |
| European (non-Finnish) | 0.000673% | 148,525 |
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.Pro12=
- Coding
- c.36G>A
- MANE Select
- NM_002578
- dbSNP
- rs142774727
- Type
- single nucleotide variant
- Location
- chrX:111123139 (GRCh38)
- Structure
- AlphaFold pLDDT 66.31 · 4 PDB
- Residue 12
- the calponin-homology (ch) domain; an α-helix
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-pro12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown