Is PAK3 p.Ala161= (c.483A>G) pathogenic?

PAK3 p.Ala161= (c.483A>G) is classified Benign/Likely benign in PAK3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-16). Rare (popmax 0.207%, afr); Associated with Inborn genetic diseases.

What condition is associated with PAK3 p.Ala161= (c.483A>G)?

PAK3 p.Ala161= (c.483A>G) is associated with Inborn genetic diseases, intellectual disability, X-linked 30 (ClinVar).

How common is PAK3 p.Ala161= (c.483A>G) in the general population?

PAK3 p.Ala161= (c.483A>G) is rare (popmax 0.207%, afr) (gnomAD).

PAK3 p.Ala161=

c.483A>G · rs146801179 · VCV367714

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.207%, afr)

Conditions

Inborn genetic diseases

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 -0.33	GERP -3.7, phastCons 0.002
Overall
CADD	4.076	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.207% African / African-American · 118/57,111 alleles

Filtering AF 0.176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.165%

Overall 0.0295% 355/1,205,216 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.207%	484
Middle Eastern	0.161%	620
Remaining individualsnot grpmax-eligible	0.0653%	1,531
Admixed American	0.0417%	2,400
European (non-Finnish)	0.0202%	4,951

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.Ala161=
Coding: c.483A>G
MANE Select: NM_001354046 · reported on NM_002578
dbSNP: rs146801179
Type: single nucleotide variant
Location: chrX:111162929 (GRCh38)
Structure: AlphaFold pLDDT 66.31 · 4 PDB

Full PAK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability, X-linked 30

Similar variants

PAK3 p.Arg100Ter Pathogenic/Likely pathogenic ★★ same condition
PAK3 p.Arg436Ter Pathogenic/Likely pathogenic ★★ same condition
PAK3 p.Glu356Ter Pathogenic/Likely pathogenic ★★ same condition
PAK3 c.830+6T>A Uncertain significance ★★ same condition
PAK3 p.Arg493Cys Uncertain significance ★★ ⚠ same condition
PAK3 p.Gly262= Uncertain significance ★★ same condition
PAK3 p.Gly335Asp Uncertain significance ★★ ⚠ same condition
PAK3 c.276+2659T>C Benign/Likely benign ★★ same condition

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-ala161 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown