Is PAK3 p.Ala147Val (c.440C>T) pathogenic?

PAK3 p.Ala147Val (c.440C>T) is classified Uncertain significance in PAK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0917); No allele count reported in gnomAD v4.1 (AN 1,173,990); Associated with Inborn genetic diseases.

What condition is associated with PAK3 p.Ala147Val (c.440C>T)?

PAK3 p.Ala147Val (c.440C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PAK3 p.Ala147Val (c.440C>T) in the general population?

PAK3 p.Ala147Val (c.440C>T) is no allele count reported in gnomAD v4.1 (AN 1,173,990) (gnomAD).

What do computational predictors say about PAK3 p.Ala147Val (c.440C>T)?

AlphaMissense predicts likely benign (score 0.0917) — an in-silico prediction, not a clinical call.

PAK3 p.Ala147Val

c.440C>T · VCV4626859

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0917 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,173,990)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0917	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 90 kb · p 0.00047 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 A162V vs ClinVar A147V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,173,990). 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.Ala147Val
Coding: c.440C>T
MANE Select: NM_002578
Type: single nucleotide variant
Location: chrX:111152419 (GRCh38)
Structure: AlphaFold pLDDT 66.31 · 4 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PAK3 p.Ala147Thr Uncertain significance ★ ⚠ same residue
PAK3 p.Arg436Ter Pathogenic/Likely pathogenic ★★ same condition
PAK3 c.830+6T>A Uncertain significance ★★ same condition
PAK3 c.276+2659T>C Benign/Likely benign ★★ same condition
PAK3 p.Ala161= Benign/Likely benign ★★ same condition
PAK3 p.Asn236Ser Likely benign ★★ same condition
PAK3 p.Gly4Ser Benign/Likely benign ★★ same condition
PAK3 p.Leu395= 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-ala147val (accessed [today's date]).

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