PAK1 p.Pro221=
c.663C>T · VCV4913332
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, 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 0.51 | GERP 0.15, phastCons 0.99 |
| Overall | ||
| CADD | 9.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,886 alleles
Filtering AF
0.00624%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00468%
Overall
0.00143%
23/1,612,932 alleles · ultra-rare
exomes 16/1,460,746 · genomes 7/152,186 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,321 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,226 |
| European (non-Finnish) | 0.00102% | 98,256 |
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.Pro221=
- Coding
- c.663C>T
- MANE Select
- NM_002576
- Type
- single nucleotide variant
- Location
- chr11:77355777 (GRCh38)
- Gene constraint
- LOEUF 0.705 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 73.90 · 41 PDB
- Residue 221
- the 'disordered' region
Similar variants
- PAK1 p.Pro221Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown