Is PAK2 p.Lys138= (c.414A>G) pathogenic?

PAK2 p.Lys138= (c.414A>G) is classified Likely benign in PAK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-08). Low-frequency (popmax 2.36%, amr); Associated with PAK2-related disorder.

What condition is associated with PAK2 p.Lys138= (c.414A>G)?

PAK2 p.Lys138= (c.414A>G) is associated with PAK2-related disorder (ClinVar).

How common is PAK2 p.Lys138= (c.414A>G) in the general population?

PAK2 p.Lys138= (c.414A>G) is low-frequency (popmax 2.36%, amr) (gnomAD).

PAK2 p.Lys138=

c.414A>G · rs73205842 · VCV3042971

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.36%, amr)

Conditions

PAK2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -5.9, phastCons 0.32
Overall
CADD	2.897	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.36% Admixed American · 1,155/48,898 alleles

Filtering AF 2.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.2%

Overall 1.01% 15,449/1,536,382 alleles · low-frequency exomes 15,449/1,384,390 · genomes 0/151,992 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.36%	42
South Asian	1.67%	60
Ashkenazi Jewishnot grpmax-eligible	1.62%	62
Remaining individualsnot grpmax-eligible	1.06%	94
East Asian	1.05%	95
Middle Eastern	1.01%	99
European (non-Finnish)	0.939%	106
Finnishnot grpmax-eligible	0.773%	129
African / African-American	0.341%	293

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.Lys138=
Coding: c.414A>G
MANE Select: NM_002577
dbSNP: rs73205842
Type: single nucleotide variant
Location: chr3:196803142 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI 0.83 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 75.06 · 9 PDB

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

Disease context

PAK2-related disorder

Similar variants

PAK2 c.935+1G>T Uncertain significance same condition
PAK2 p.Gly329Val Uncertain significance ⚠ same condition
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

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-lys138 (accessed [today's date]).

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