Is PAK3 p.Arg100Ter (c.298C>T) pathogenic?

PAK3 p.Arg100Ter (c.298C>T) is classified Pathogenic/Likely pathogenic in PAK3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-11-09). Absent from gnomAD v4.1; Associated with PAK3-related disorder.

What condition is associated with PAK3 p.Arg100Ter (c.298C>T)?

PAK3 p.Arg100Ter (c.298C>T) is associated with PAK3-related disorder, intellectual disability, X-linked 30 (ClinVar).

How common is PAK3 p.Arg100Ter (c.298C>T) in the general population?

PAK3 p.Arg100Ter (c.298C>T) is absent from gnomAD v4.1 (gnomAD).

PAK3 p.Arg100Ter

c.298C>T · rs780775497 · VCV438299

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,204,348)

Conditions

PAK3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.2, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,204,348). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PAK3
Protein: p.Arg100Ter
Coding: c.298C>T
MANE Select: NM_001354046 · reported on NM_002578
dbSNP: rs780775497
Type: single nucleotide variant
Location: chrX:111147758 (GRCh38)
Structure: AlphaFold pLDDT 66.31 · 4 PDB
Residue 100: the calponin-homology (ch) domain

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

Disease context

PAK3-related disorder

Also linked: intellectual disability, X-linked 30

Similar variants

PAK3 p.Arg100Gln Uncertain significance ★ ⚠ same residue
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-arg100ter (accessed [today's date]).

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