Is PAK3 p.Arg487fs (c.1460_1461del) pathogenic?

PAK3 p.Arg487fs (c.14601461del) is classified Likely pathogenic in PAK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-17). Associated with PAK3-related disorder.

What condition is associated with PAK3 p.Arg487fs (c.1460_1461del)?

PAK3 p.Arg487fs (c.1460_1461del) is associated with PAK3-related disorder (ClinVar).

PAK3 p.Arg487fs

c.1460_1461del · VCV4952412

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

PAK3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.3	GERP -4.2

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

Variant & gene context

Gene: PAK3
Protein: p.Arg487fs
Coding: c.1460_1461del
MANE Select: NM_002578
Type: Microsatellite
Location: chrX:111216469 (GRCh38)
Structure: AlphaFold pLDDT 66.31 · 4 PDB
Residue 487: the ph domain

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

Disease context

PAK3-related disorder

Similar variants

ARHGEF7 p.Leu487= Benign ★★ same residue
PAK3 p.Arg100Ter Pathogenic/Likely pathogenic ★★ same condition
PAK3 c.431-1G>A Likely pathogenic ★ same condition
PAK3 p.Gln135Arg Uncertain significance ★ ⚠ same condition
PAK3 c.1211-1G>T Uncertain significance same condition
PAK3 p.Gly396Arg Uncertain significance ⚠ same condition
PAK3 c.601-3dup Likely benign same condition
PAK3 p.Glu182del 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-arg487fs (accessed [today's date]).

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