Is CDC42EP1 p.Phe378Val (c.1132T>G) pathogenic?

CDC42EP1 p.Phe378Val (c.1132T>G) is classified Uncertain significance in CDC42EP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: likely benign (0.2681); Absent from gnomAD v4.1.

How common is CDC42EP1 p.Phe378Val (c.1132T>G) in the general population?

CDC42EP1 p.Phe378Val (c.1132T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42EP1 p.Phe378Val (c.1132T>G)?

AlphaMissense predicts likely benign (score 0.2681) — an in-silico prediction, not a clinical call.

CDC42EP1 p.Phe378Val

c.1132T>G · VCV3265013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2681 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,496,382)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2681	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 2,467 bp · p 0.23 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,496,382). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDC42EP1
Protein: p.Phe378Val
Coding: c.1132T>G
MANE Select: NM_152243
Type: single nucleotide variant
Location: chr22:37568776 (GRCh38)
Gene constraint: LOEUF 1.863 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.46
Residue 378: the 'disordered' region

Full CDC42EP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC42EP1 p.Leu344Pro Uncertain significance ★★ ⚠ same type
CDC42EP1 p.Glu184= Benign ★★ same type
CDC42EP1 p.Gly308= Benign ★★ same type
CDC42EP1 p.His67= Benign ★★ same type
CDC42EP1 p.Leu194= Benign ★★ same type
CDC42EP1 p.Thr372= Benign ★★ same type
CDC42EP1 p.Ala10Thr Uncertain significance ★ ⚠ same type
CDC42EP1 p.Ala129Ser Uncertain significance ★ ⚠ 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/cdc42ep1-p-phe378val (accessed [today's date]).

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