Is CDC42 p.Asp76Asn (c.226G>A) pathogenic?

CDC42 p.Asp76Asn (c.226G>A) is classified Uncertain significance in CDC42 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-19). AlphaMissense: likely pathogenic (0.8322); Absent from gnomAD v4.1; Associated with Takenouchi-Kosaki syndrome.

What condition is associated with CDC42 p.Asp76Asn (c.226G>A)?

CDC42 p.Asp76Asn (c.226G>A) is associated with Takenouchi-Kosaki syndrome (ClinVar).

How common is CDC42 p.Asp76Asn (c.226G>A) in the general population?

CDC42 p.Asp76Asn (c.226G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42 p.Asp76Asn (c.226G>A)?

AlphaMissense predicts likely pathogenic (score 0.8322) — an in-silico prediction, not a clinical call.

CDC42 p.Asp76Asn

c.226G>A · VCV4681126

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8322 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Takenouchi-Kosaki syndrome

Computational evidence

Protein change
AlphaMissense	0.8322	likely pathogenic
REVEL	0.502	indeterminate
SaProt	LLR -13.07	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	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	29.6	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.Asp76Asn
Coding: c.226G>A
MANE Select: NM_001791
Type: single nucleotide variant
Location: chr1:22086486 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 48 PDB
Residue 76: a β-strand

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.Asp76Val Likely pathogenic ★ same residue
CDC42 p.Asp76= Likely benign ★★ same residue
CDC42 p.Asp76Gly Uncertain significance ★ ⚠ 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

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-asp76asn (accessed [today's date]).

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