Is PAK3 p.Asp3= (c.9C>T) pathogenic?

PAK3 p.Asp3= (c.9C>T) is classified Benign in PAK3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-31). Ultra-rare (popmax 0.0106%, afr); Associated with intellectual disability, X-linked 30.

What condition is associated with PAK3 p.Asp3= (c.9C>T)?

PAK3 p.Asp3= (c.9C>T) is associated with intellectual disability, X-linked 30 (ClinVar).

How common is PAK3 p.Asp3= (c.9C>T) in the general population?

PAK3 p.Asp3= (c.9C>T) is ultra-rare (popmax 0.0106%, afr) (gnomAD).

PAK3 p.Asp3=

c.9C>T · rs745645606 · VCV914027

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, afr)

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 1.8	phastCons 0.93
Overall
CADD	9.666	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0106% African / African-American · 6/56,708 alleles

Filtering AF 0.00459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00425% 51/1,199,883 alleles · ultra-rare exomes 46/1,088,842 · genomes 5/111,041 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0106%	9,451
South Asian	0.00531%	18,850
Ashkenazi Jewishnot grpmax-eligible	0.00456%	21,951
European (non-Finnish)	0.0044%	22,732
Remaining individualsnot grpmax-eligible	0.00423%	23,653

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.Asp3=
Coding: c.9C>T
MANE Select: NM_002578
dbSNP: rs745645606
Type: single nucleotide variant
Location: chrX:111123112 (GRCh38)
Structure: AlphaFold pLDDT 66.31 · 4 PDB
Residue 3: the calponin-homology (ch) domain; an α-helix

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-asp3 (accessed [today's date]).

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