PAK3 p.Pro441=
c.1323G>A · rs61733749 · VCV436145
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0158%, 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 -5.7 | GERP -4.2 |
| Overall | ||
| CADD | 1.579 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0158%
African / African-American · 9/57,055 alleles
Filtering AF
0.00819%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00615%
Overall
0.00391%
47/1,203,174 alleles · ultra-rare
exomes 39/1,091,538 · genomes 8/111,636 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0158% | 6,339 |
| Finnishnot grpmax-eligible | 0.00644% | 15,530 |
| European (non-Finnish) | 0.0036% | 27,787 |
| East Asian | 0.00297% | 33,707 |
| Admixed American | 0.00219% | 45,684 |
| Remaining individualsnot grpmax-eligible | 0.00211% | 47,393 |
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.Pro441=
- Coding
- c.1323G>A
- MANE Select
- NM_002578
- dbSNP
- rs61733749
- Type
- single nucleotide variant
- Location
- chrX:111196556 (GRCh38)
- Structure
- AlphaFold pLDDT 66.31 · 4 PDB
- Residue 441
- the dh domain; an α-helix
Similar variants
- PAK3 p.Pro441Leu Uncertain significance ★ ⚠ same residue
- PAK3 p.Pro441Thr Uncertain significance ★ ⚠ same residue
- 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
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-pro441 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown