Is CDC42 p.Ala130Val (c.389C>T) pathogenic?

CDC42 p.Ala130Val (c.389C>T) is classified Uncertain significance in CDC42 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely benign (0.1412); Very rare (popmax 8.48e-05%, nfe); Associated with CDC42-related disorder.

What condition is associated with CDC42 p.Ala130Val (c.389C>T)?

CDC42 p.Ala130Val (c.389C>T) is associated with CDC42-related disorder (ClinVar).

How common is CDC42 p.Ala130Val (c.389C>T) in the general population?

CDC42 p.Ala130Val (c.389C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDC42 p.Ala130Val (c.389C>T)?

AlphaMissense predicts likely benign (score 0.1412) — an in-silico prediction, not a clinical call.

CDC42 p.Ala130Val

c.389C>T · rs1235149233 · VCV2631107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1412 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CDC42-related disorder

Computational evidence

Protein change
AlphaMissense	0.1412	likely benign
REVEL	0.332	indeterminate
SaProt	LLR -10.98	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 4,828 bp · p 3e-11 · regional, not allelic
Overall
CADD	28.2	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,900 alleles

Overall 6.84e-05% 1/1,461,750 alleles · very rare

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: CDC42
Protein: p.Ala130Val
Coding: c.389C>T
MANE Select: NM_001791
dbSNP: rs1235149233
Type: single nucleotide variant
Location: chr1:22086769 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 48 PDB
Residue 130: an α-helix

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

Disease context

CDC42-related disorder

Similar variants

CDC42 p.Arg68Gln Pathogenic ★★ same condition
CDC42 p.Tyr23Cys Pathogenic ★★ same condition
CDC42 p.Tyr64Asn Likely pathogenic ★ same condition
CDC42 p.Pro34Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
CDC42 p.Ser185fs Likely pathogenic ★ same condition
CDC42 p.Ala159Val Pathogenic ★★ same type
CDC42 p.Arg186Cys Pathogenic ★★ ⚠ same type
CDC42 p.Arg66Gly 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-ala130val (accessed [today's date]).

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