PAK1 p.Ser133=
c.399G>A · VCV4913336
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00432%, 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 -0.2 | GERP -2.6, phastCons 0.32 |
| Overall | ||
| CADD | 11.08 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00432%
European (non-Finnish) · 51/1,179,826 alleles
Filtering AF
0.00334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00302%
Overall
0.00347%
56/1,613,824 alleles · very rare
exomes 54/1,461,536 · genomes 2/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00432% | 23,134 |
| African / African-American | 0.00267% | 37,513 |
| South Asian | 0.0022% | 45,530 |
| Finnishnot grpmax-eligible | 0.00156% | 64,004 |
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.Ser133=
- Coding
- c.399G>A
- MANE Select
- NM_002576
- Type
- single nucleotide variant
- Location
- chr11:77379281 (GRCh38)
- Gene constraint
- LOEUF 0.705 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 73.90 · 41 PDB
- Residue 133
- the 'autoregulatory region' region; an α-helix
Similar variants
- PAK1 p.Ser133Pro Likely pathogenic ★ same residue
- PAK1 p.Ser133Leu 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
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-ser133 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown