Is PAK3 p.Lys306= (c.918G>A) pathogenic?

PAK3 p.Lys306= (c.918G>A) is classified Benign/Likely benign in PAK3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-28). Ultra-rare (popmax 0.0219%, amr); Associated with intellectual disability, X-linked 30.

What condition is associated with PAK3 p.Lys306= (c.918G>A)?

PAK3 p.Lys306= (c.918G>A) is associated with intellectual disability, X-linked 30 (ClinVar).

How common is PAK3 p.Lys306= (c.918G>A) in the general population?

PAK3 p.Lys306= (c.918G>A) is ultra-rare (popmax 0.0219%, amr) (gnomAD).

PAK3 p.Lys306=

c.918G>A · rs151056810 · VCV761365

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0219%, amr)

Conditions

intellectual disability, X-linked 30

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 4.6	GERP -0.26, phastCons 1
Overall
CADD	8.302	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0219% Admixed American · 10/45,665 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0134%

Overall 0.0137% 161/1,171,801 alleles · ultra-rare exomes 144/1,060,187 · genomes 17/111,614 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0219%	4,567
European (non-Finnish)	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.013%	7,720
African / African-American	0.00532%	18,810

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.Lys306=
Coding: c.918G>A
MANE Select: NM_002578
dbSNP: rs151056810
Type: single nucleotide variant
Location: chrX:111192544 (GRCh38)
Structure: AlphaFold pLDDT 66.31 · 4 PDB
Residue 306: the dh domain; a β-strand

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

Disease context

intellectual disability, X-linked 30 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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 p.Arg493Cys Uncertain significance ★★ ⚠ same condition
PAK3 p.Gly262= Uncertain significance ★★ same condition
PAK3 p.Gly335Asp Uncertain significance ★★ ⚠ same condition
PAK3 c.431-26A>G Benign ★★ same condition
PAK3 p.Ala161= 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-lys306 (accessed [today's date]).

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