PAK1 p.Pro428=
c.1284A>T · rs142211771 · VCV2642184
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0779%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.037 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -9.4 | GERP -2.9 |
| Overall | ||
| CADD | 5.283 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0779%
European (non-Finnish) · 919/1,179,940 alleles
Filtering AF
0.0737%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.072%
Overall
0.0589%
951/1,614,122 alleles · ultra-rare
exomes 904/1,461,766 · genomes 47/152,356 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0779% | 1,284 |
| African / African-American | 0.0187% | 5,362 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,683 |
| Admixed American | 0.00666% | 15,006 |
| South Asian | 0.0022% | 45,537 |
| Finnishnot grpmax-eligible | 0.00156% | 64,046 |
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.Pro428=
- Coding
- c.1284A>T
- MANE Select
- NM_002576
- dbSNP
- rs142211771
- Type
- single nucleotide variant
- Location
- chr11:77336215 (GRCh38)
- Gene constraint
- LOEUF 0.705 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 73.90 · 41 PDB
- Residue 428
- the protein kinase domain; an α-helix
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-pro428 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown