Is PAK2 p.Asn445Ser (c.1334A>G) pathogenic?

PAK2 p.Asn445Ser (c.1334A>G) is classified Uncertain significance in PAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: ambiguous (0.475); Very rare (popmax 8.65e-05%, nfe).

How common is PAK2 p.Asn445Ser (c.1334A>G) in the general population?

PAK2 p.Asn445Ser (c.1334A>G) is very rare (popmax 8.65e-05%, nfe) (gnomAD).

What do computational predictors say about PAK2 p.Asn445Ser (c.1334A>G)?

AlphaMissense predicts ambiguous (score 0.475) — an in-silico prediction, not a clinical call.

PAK2 p.Asn445Ser

c.1334A>G · VCV4564074

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.65e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.475	ambiguous
REVEL	0.455	indeterminate
SaProt	LLR -12.92	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.9, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 13 kb · p 5.4e-23 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.65e-05% European (non-Finnish) · 1/1,155,858 alleles

Overall 6.35e-05% 1/1,575,084 alleles · very rare exomes 1/1,422,736 · genomes 0/152,348 · joint denominator

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: PAK2
Protein: p.Asn445Ser
Coding: c.1334A>G
MANE Select: NM_002577
Type: single nucleotide variant
Location: chr3:196820551 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI 0.83 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 75.06 · 9 PDB
Residue 445: the protein kinase domain; a turn

Full PAK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PAK2 p.Asp425Asn Likely pathogenic ★ same type
PAK2 p.Gln279Pro Likely pathogenic ★ same type
PAK2 p.Ala347Thr Uncertain significance ★ same type
PAK2 p.Ala90Gly Uncertain significance ★ same type
PAK2 p.Arg104Gln Uncertain significance ★ ⚠ same type
PAK2 p.Arg186Leu Uncertain significance ★ ⚠ same type
PAK2 p.Arg350Gly Uncertain significance ★ ⚠ same type
PAK2 p.Arg524His 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/pak2-p-asn445ser (accessed [today's date]).

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