Is PAK2 p.Asp484Val (c.1451A>T) pathogenic?

PAK2 p.Asp484Val (c.1451A>T) is classified Uncertain significance in PAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: ambiguous (0.4747); Ultra-rare (popmax 0.0108%, nfe).

How common is PAK2 p.Asp484Val (c.1451A>T) in the general population?

PAK2 p.Asp484Val (c.1451A>T) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

What do computational predictors say about PAK2 p.Asp484Val (c.1451A>T)?

AlphaMissense predicts ambiguous (score 0.4747) — an in-silico prediction, not a clinical call.

PAK2 p.Asp484Val

c.1451A>T · rs761446581 · VCV2240722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4747 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4747	ambiguous
REVEL	0.611	indeterminate
SaProt	LLR -14.30	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 1,148 bp · p 0.0027 · regional, not allelic
Overall
CADD	32.0	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 0.0108% European (non-Finnish) · 127/1,179,136 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00864%

Overall 0.00806% 130/1,612,396 alleles · ultra-rare exomes 127/1,460,228 · genomes 3/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0108%	9,285
African / African-American	0.00267%	37,431
Remaining individualsnot grpmax-eligible	0.0016%	62,428

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.Asp484Val
Coding: c.1451A>T
MANE Select: NM_002577
dbSNP: rs761446581
Type: single nucleotide variant
Location: chr3:196827296 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI 0.83 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 75.06 · 9 PDB
Residue 484: the protein kinase domain

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-asp484val (accessed [today's date]).

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