Is PAK1 p.Thr97= (c.291G>A) pathogenic?

PAK1 p.Thr97= (c.291G>A) is classified Benign in PAK1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-02-21). Low-frequency (popmax 1.81%, nfe); Associated with PAK1-related disorder.

What condition is associated with PAK1 p.Thr97= (c.291G>A)?

PAK1 p.Thr97= (c.291G>A) is associated with PAK1-related disorder (ClinVar).

How common is PAK1 p.Thr97= (c.291G>A) in the general population?

PAK1 p.Thr97= (c.291G>A) is low-frequency (popmax 1.81%, nfe) (gnomAD).

PAK1 p.Thr97=

c.291G>A · rs1130059 · VCV3038097

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.81%, nfe)

Conditions

PAK1-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 -1.3	GERP -3.8, phastCons 0.001
Overall
CADD	16.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.81% European (non-Finnish) · 21,260/1,175,710 alleles

Filtering AF 1.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.78%

Overall 1.62% 26,000/1,609,066 alleles · low-frequency exomes 23,935/1,456,850 · genomes 2,065/152,216 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	3.36%	30
European (non-Finnish)grpmax	1.81%	55
Remaining individualsnot grpmax-eligible	1.74%	57
Middle Eastern	1.49%	67
South Asian	1.04%	96
African / African-American	0.947%	106
Admixed American	0.902%	111
Finnishnot grpmax-eligible	0.578%	173
Amishnot grpmax-eligible	0.33%	303
East Asian	0.00446%	22,424

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PAK1
Protein: p.Thr97=
Coding: c.291G>A
MANE Select: NM_002576
dbSNP: rs1130059
Type: single nucleotide variant
Location: chr11:77379894 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 73.90 · 41 PDB
Residue 97: the 'autoregulatory region' region; a β-strand; the 'gtpase-binding' region

Full PAK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PAK1-related disorder

Similar variants

PAK1 p.Pro121Leu Pathogenic ★★ same condition
PAK1 p.Leu465Phe Likely pathogenic ★ same condition
PAK1 p.Ala512= Likely benign same condition
PAK1 p.Leu397= Likely benign same condition
PAK1 p.Gly409fs Uncertain significance same condition
PAK1 p.Ile476Thr Pathogenic/Likely pathogenic ★★ same type
PAK1 p.Leu470Arg Likely pathogenic ★★ same type
PAK1 p.Met143Thr Likely pathogenic ★★ 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/pak1-p-thr97 (accessed [today's date]).

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