Is CDC42EP1 p.Pro102Leu (c.305C>T) pathogenic?

CDC42EP1 p.Pro102Leu (c.305C>T) is classified Uncertain significance in CDC42EP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1005); Very rare (popmax 0.00267%, afr).

How common is CDC42EP1 p.Pro102Leu (c.305C>T) in the general population?

CDC42EP1 p.Pro102Leu (c.305C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CDC42EP1 p.Pro102Leu (c.305C>T)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

CDC42EP1 p.Pro102Leu

c.305C>T · rs1036124428 · VCV3140920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -7.14	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 3.3	GERP 0.63, phastCons 0.99
Regional constraint	o/e 1.05	unconstrained · MANE · 2,467 bp · p 0.23 · regional, not allelic
Overall
CADD	17.61	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

Grpmax group 0.00267% African / African-American · 2/74,768 alleles

Filtering AF 0.000767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000608%

Overall 0.00106% 17/1,604,022 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,384
European (non-Finnish)	0.00128%	78,302

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: CDC42EP1
Protein: p.Pro102Leu
Coding: c.305C>T
MANE Select: NM_152243
dbSNP: rs1036124428
Type: single nucleotide variant
Location: chr22:37566654 (GRCh38)
Gene constraint: LOEUF 1.863 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.46

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-pro102leu (accessed [today's date]).

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