Is CDC42 p.Pro34Leu (c.101C>T) pathogenic?

CDC42 p.Pro34Leu (c.101C>T) is classified Uncertain significance in CDC42 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-31). AlphaMissense: likely pathogenic (0.9971); Absent from gnomAD v4.1.

How common is CDC42 p.Pro34Leu (c.101C>T) in the general population?

CDC42 p.Pro34Leu (c.101C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42 p.Pro34Leu (c.101C>T)?

AlphaMissense predicts likely pathogenic (score 0.9971) — an in-silico prediction, not a clinical call.

CDC42 p.Pro34Leu

c.101C>T · rs1645575465 · VCV1304835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9971 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9971	likely pathogenic
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -16.41	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 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.09	constrained · MANE · 8,206 bp · p 1.3e-23 · regional, not allelic
Overall
CADD	29.8	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.Pro34Leu
Coding: c.101C>T
MANE Select: NM_001791
dbSNP: rs1645575465
Type: single nucleotide variant
Location: chr1:22078579 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 48 PDB
Residue 34: an α-helix

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

Similar variants

CDC42 p.Pro34Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CDC42 p.Pro34= Likely benign ★ 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

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-pro34leu (accessed [today's date]).

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