PAK1 p.Pro12=
c.36C>G · rs775839991 · VCV3025439
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 1.2 | GERP -0.68, phastCons 1 |
| Overall | ||
| CADD | 8.795 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/90,972 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000496%
8/1,613,270 alleles · very rare
exomes 8/1,461,066 · genomes 0/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,486 |
| Admixed American | 0.00167% | 59,960 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,452 |
| European (non-Finnish) | 0.000339% | 294,876 |
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
- PAK1
- Protein
- p.Pro12=
- Coding
- c.36C>G
- MANE Select
- NM_002576
- dbSNP
- rs775839991
- Type
- single nucleotide variant
- Location
- chr11:77392485 (GRCh38)
- Gene constraint
- LOEUF 0.705 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 73.90 · 41 PDB
- Residue 12
- the 'disordered' region
Similar variants
- PAK1 p.Ile476Thr Pathogenic/Likely pathogenic ★★ same type
- PAK1 p.Leu470Arg Likely pathogenic ★★ same type
- PAK1 p.Met143Thr Likely pathogenic ★★ same type
- PAK1 p.Pro121Leu Pathogenic ★★ same type
- PAK1 p.Pro121Ser Pathogenic/Likely pathogenic ★★ same type
- PAK1 p.Ala524Pro Uncertain significance ★★ ⚠ same type
- PAK1 p.Arg215Trp Uncertain significance ★★ ⚠ same type
- PAK1 p.Arg258Ter 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/pak1-p-pro12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown