Is PAK3 p.Pro34Leu (c.101C>T) pathogenic?

PAK3 p.Pro34Leu (c.101C>T) is classified Uncertain significance in PAK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-10-22). AlphaMissense: likely pathogenic (0.8638); Very rare (popmax 0.00236%, nfe).

How common is PAK3 p.Pro34Leu (c.101C>T) in the general population?

PAK3 p.Pro34Leu (c.101C>T) is very rare (popmax 0.00236%, nfe) (gnomAD).

What do computational predictors say about PAK3 p.Pro34Leu (c.101C>T)?

AlphaMissense predicts likely pathogenic (score 0.8638) — an in-silico prediction, not a clinical call.

PAK3 p.Pro34Leu

c.101C>T · rs370566075 · VCV197746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8638 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00236%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8638	likely pathogenic
REVEL	0.533	indeterminate
SaProt	LLR -10.61	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 90 kb · p 0.00047 · regional, not allelic
Overall
CADD	28.2	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00236% European (non-Finnish) · 21/890,709 alleles

Filtering AF 0.00152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00129%

Overall 0.00182% 22/1,205,484 alleles · very rare exomes 21/1,093,059 · genomes 1/112,425 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00236%	42,415
African / African-American	0.00175%	57,228

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.Pro34Leu
Coding: c.101C>T
MANE Select: NM_002578
dbSNP: rs370566075
Type: single nucleotide variant
Location: chrX:111123204 (GRCh38)
Structure: AlphaFold pLDDT 66.31 · 4 PDB
Residue 34: the calponin-homology (ch) domain; an α-helix

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

Similar variants

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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-pro34leu (accessed [today's date]).

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