Is CDC42 p.Pro69Leu (c.206C>T) pathogenic?

CDC42 p.Pro69Leu (c.206C>T) is classified Uncertain significance in CDC42 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely pathogenic (0.9856); Absent from gnomAD v4.1; Associated with Takenouchi-Kosaki syndrome.

What condition is associated with CDC42 p.Pro69Leu (c.206C>T)?

CDC42 p.Pro69Leu (c.206C>T) is associated with Takenouchi-Kosaki syndrome (ClinVar).

How common is CDC42 p.Pro69Leu (c.206C>T) in the general population?

CDC42 p.Pro69Leu (c.206C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42 p.Pro69Leu (c.206C>T)?

AlphaMissense predicts likely pathogenic (score 0.9856) — an in-silico prediction, not a clinical call.

CDC42 p.Pro69Leu

c.206C>T · rs1645663343 · VCV3237457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9856 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Takenouchi-Kosaki syndrome

Computational evidence

Protein change
AlphaMissense	0.9856	likely pathogenic
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -16.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.09	constrained · MANE · 8,206 bp · p 1.3e-23 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CDC42
Protein: p.Pro69Leu
Coding: c.206C>T
MANE Select: NM_001791
dbSNP: rs1645663343
Type: single nucleotide variant
Location: chr1:22086466 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 48 PDB
Residue 69: an α-helix

Full CDC42 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Takenouchi-Kosaki syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDC42 p.Pro69= Benign ★ same residue
CDC42 p.Arg66Gly Pathogenic ★★ same condition
CDC42 p.Arg68Gln Pathogenic ★★ same condition
CDC42 p.Cys81Phe Likely pathogenic ★★ same condition
CDC42 p.Glu171Lys Pathogenic ★★ same condition
CDC42 p.Ser83Pro Pathogenic ★★ same condition
CDC42 p.Tyr23Cys Pathogenic ★★ same condition
CDC42 p.Tyr64Cys Pathogenic/Likely pathogenic ★★ same condition

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/cdc42-p-pro69leu (accessed [today's date]).

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