Is PAK3 p.Val282Ala (c.845T>C) pathogenic?

PAK3 p.Val282Ala (c.845T>C) is classified Uncertain significance in PAK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-08). AlphaMissense: likely pathogenic (0.9998); No allele count reported in gnomAD v4.1 (AN 1,124,992).

How common is PAK3 p.Val282Ala (c.845T>C) in the general population?

PAK3 p.Val282Ala (c.845T>C) is no allele count reported in gnomAD v4.1 (AN 1,124,992) (gnomAD).

What do computational predictors say about PAK3 p.Val282Ala (c.845T>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

PAK3 p.Val282Ala

c.845T>C · VCV3359519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,124,992)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 1% in PAK3
REVEL	0.933	strongly pathogenic-leaning
SaProt	LLR -12.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 90 kb · p 0.00047 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V297A vs ClinVar V282A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,124,992). 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.Val282Ala
Coding: c.845T>C
MANE Select: NM_002578
Type: single nucleotide variant
Location: chrX:111192141 (GRCh38)
Structure: AlphaFold pLDDT 66.31 · 4 PDB
Residue 297 UniProt numbering: the dh domain; an α-helix

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

Similar variants

PAK3 p.Arg100Ter Pathogenic/Likely pathogenic ★★ same type
PAK3 p.Arg436Ter Pathogenic/Likely pathogenic ★★ same type
PAK3 p.Glu356Ter Pathogenic/Likely pathogenic ★★ same type
PAK3 c.830+6T>A Uncertain significance ★★ same type
PAK3 p.Ala490Thr Uncertain significance ★★ ⚠ same type
PAK3 p.Arg493Cys Uncertain significance ★★ ⚠ same type
PAK3 p.Arg498Cys Uncertain significance ★★ ⚠ same type
PAK3 p.Asn185Thr 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-val282ala (accessed [today's date]).

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