Is PAK2 p.Gln279Pro (c.836A>C) pathogenic?

PAK2 p.Gln279Pro (c.836A>C) is classified Likely pathogenic in PAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with Knobloch syndrome 2.

What condition is associated with PAK2 p.Gln279Pro (c.836A>C)?

PAK2 p.Gln279Pro (c.836A>C) is associated with Knobloch syndrome 2 (ClinVar).

How common is PAK2 p.Gln279Pro (c.836A>C) in the general population?

PAK2 p.Gln279Pro (c.836A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PAK2 p.Gln279Pro (c.836A>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

PAK2 p.Gln279Pro

c.836A>C · VCV3362907

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Knobloch syndrome 2

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic ✓ concordant with ClinVar · top 9% in PAK2
REVEL	0.63	indeterminate
SaProt	LLR -14.00	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PAK2
Protein: p.Gln279Pro
Coding: c.836A>C
MANE Select: NM_002577
Type: single nucleotide variant
Location: chr3:196812752 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI 0.83 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 75.06 · 9 PDB
Residue 279: the protein kinase domain; a β-strand

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

Disease context

Knobloch syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PAK2 p.Asp425Asn Likely pathogenic ★ same condition
PAK2 p.Ile111Thr Uncertain significance ★ ⚠ same condition
PAK2 p.Lys492Asn Uncertain significance ★ ⚠ same condition
PAK2 p.Val437Ile Uncertain significance ★ ⚠ same condition
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

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-gln279pro (accessed [today's date]).

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