Is CDC42 p.Glu171Lys (c.511G>A) pathogenic?

CDC42 p.Glu171Lys (c.511G>A) is classified Pathogenic in CDC42 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-02-09). AlphaMissense: likely pathogenic (0.9278); Absent from gnomAD v4.1; Associated with Noonan-like syndrome.

What condition is associated with CDC42 p.Glu171Lys (c.511G>A)?

CDC42 p.Glu171Lys (c.511G>A) is associated with Noonan-like syndrome, Takenouchi-Kosaki syndrome (ClinVar).

How common is CDC42 p.Glu171Lys (c.511G>A) in the general population?

CDC42 p.Glu171Lys (c.511G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42 p.Glu171Lys (c.511G>A)?

AlphaMissense predicts likely pathogenic (score 0.9278) — an in-silico prediction, not a clinical call.

CDC42 p.Glu171Lys

c.511G>A · rs1553196539 · VCV487654

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Noonan-like syndrome

Computational evidence

Protein change
AlphaMissense	0.9278	likely pathogenic ✓ concordant with ClinVar
REVEL	0.768	pathogenic-leaning
SaProt	LLR -17.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	GERP 2.4, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 4,828 bp · p 3e-11 · regional, not allelic
Overall
CADD	26.6	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: CDC42
Protein: p.Glu171Lys
Coding: c.511G>A
MANE Select: NM_001791
dbSNP: rs1553196539
Type: single nucleotide variant
Location: chr1:22091452 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 48 PDB
Residue 171: an α-helix

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

Disease context

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

Also linked: Takenouchi-Kosaki syndrome

Similar variants

CDC42 p.Arg66Gly Pathogenic ★★ same condition
CDC42 p.Arg68Gln Pathogenic ★★ same condition
CDC42 p.Cys81Phe Likely pathogenic ★★ same condition
CDC42 p.Ser83Pro Pathogenic ★★ same condition
CDC42 p.Tyr23Cys Pathogenic ★★ same condition
CDC42 p.Tyr64Cys Pathogenic/Likely pathogenic ★★ same condition
CDC42 p.Asp76Asn Uncertain significance ★★ ⚠ same condition
CDC42 p.Asp170= Likely benign ★★ 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-glu171lys (accessed [today's date]).

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