Is PAK4 p.Ala13Ser (c.37G>T) pathogenic?

PAK4 p.Ala13Ser (c.37G>T) is classified Uncertain significance in PAK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.139); Ultra-rare (popmax 0.0167%, amr).

How common is PAK4 p.Ala13Ser (c.37G>T) in the general population?

PAK4 p.Ala13Ser (c.37G>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about PAK4 p.Ala13Ser (c.37G>T)?

AlphaMissense predicts likely benign (score 0.139) — an in-silico prediction, not a clinical call.

PAK4 p.Ala13Ser

c.37G>T · rs753086242 · VCV3208043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.139 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.139	likely benign
REVEL	0.447	indeterminate
SaProt	LLR -5.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Overall
CADD	25.5	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/59,968 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.00155% 25/1,613,436 alleles · ultra-rare exomes 21/1,461,640 · genomes 4/151,796 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,997
European (non-Finnish)	0.00127%	78,656

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: PAK4
Protein: p.Ala13Ser
Coding: c.37G>T
MANE Select: NM_005884
dbSNP: rs753086242
Type: single nucleotide variant
Location: chr19:39169590 (GRCh38)
Gene constraint: LOEUF 1.268 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.26 · 50 PDB
Residue 13: the crib domain; an α-helix

Full PAK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PAK4 p.Ala13Thr Uncertain significance ★ ⚠ same residue
PAK4 p.Ala13Val Uncertain significance ★ ⚠ same residue
PAK4 p.Ala573Ser Benign ★★ same type
PAK4 p.Ala109Asp Uncertain significance ★ ⚠ same type
PAK4 p.Ala111Ser Uncertain significance ★ ⚠ same type
PAK4 p.Ala125Asp Uncertain significance ★ ⚠ same type
PAK4 p.Ala154Ser Uncertain significance ★ ⚠ same type
PAK4 p.Ala197Val 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/pak4-p-ala13ser (accessed [today's date]).

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