Is CDC42 p.Arg120Lys (c.359G>A) pathogenic?

CDC42 p.Arg120Lys (c.359G>A) is classified Uncertain significance in CDC42 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). AlphaMissense: likely pathogenic (0.8578); Absent from gnomAD v4.1.

How common is CDC42 p.Arg120Lys (c.359G>A) in the general population?

CDC42 p.Arg120Lys (c.359G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42 p.Arg120Lys (c.359G>A)?

AlphaMissense predicts likely pathogenic (score 0.8578) — an in-silico prediction, not a clinical call.

CDC42 p.Arg120Lys

c.359G>A · rs2522222793 · VCV2761642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8578 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8578	likely pathogenic
REVEL	0.715	pathogenic-leaning
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 4,828 bp · p 3e-11 · regional, not allelic
Overall
CADD	32.0	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.Arg120Lys
Coding: c.359G>A
MANE Select: NM_001791
dbSNP: rs2522222793
Type: single nucleotide variant
Location: chr1:22086739 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 48 PDB
Residue 120: an α-helix

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

Similar variants

CDC42 p.Arg120Ile Uncertain significance ★ ⚠ same residue
CDC42 p.Ala159Val Pathogenic ★★ same type
CDC42 p.Arg186Cys Pathogenic ★★ ⚠ same type
CDC42 p.Arg66Gly Pathogenic ★★ same type
CDC42 p.Arg68Gln Pathogenic ★★ same type
CDC42 p.Cys81Phe Likely pathogenic ★★ same type
CDC42 p.Glu171Lys Pathogenic ★★ same type
CDC42 p.Ser83Pro 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/cdc42-p-arg120lys (accessed [today's date]).

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