Is CDC42EP5 p.Pro77Ser (c.229C>T) pathogenic?

CDC42EP5 p.Pro77Ser (c.229C>T) is classified Uncertain significance in CDC42EP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-20). AlphaMissense: likely benign (0.0788); No allele count reported in gnomAD v4.1 (AN 1,205,202).

How common is CDC42EP5 p.Pro77Ser (c.229C>T) in the general population?

CDC42EP5 p.Pro77Ser (c.229C>T) is no allele count reported in gnomAD v4.1 (AN 1,205,202) (gnomAD).

What do computational predictors say about CDC42EP5 p.Pro77Ser (c.229C>T)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

CDC42EP5 p.Pro77Ser

c.229C>T · rs2514701981 · VCV2268234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,205,202)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -8.49	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 2.4	GERP 1.5, phastCons 0.74
Regional constraint	o/e 1.13	unconstrained · MANE · 443 bp · p 0.045 · regional, not allelic
Overall
CADD	17.4	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 1,205,202). 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: CDC42EP5
Protein: p.Pro77Ser
Coding: c.229C>T
MANE Select: NM_145057
dbSNP: rs2514701981
Type: single nucleotide variant
Location: chr19:54465319 (GRCh38)
Gene constraint: LOEUF 1.961 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09
Residue 77: the 'disordered' region

Full CDC42EP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC42EP5 p.Pro77Leu Uncertain significance ★ ⚠ same residue
CDC42EP5 p.Ala116Thr Uncertain significance ★ ⚠ same type
CDC42EP5 p.Ala121Val Uncertain significance ★ ⚠ same type
CDC42EP5 p.Ala132Asp Uncertain significance ★ ⚠ same type
CDC42EP5 p.Ala62Thr Uncertain significance ★ ⚠ same type
CDC42EP5 p.Ala67Asp Uncertain significance ★ ⚠ same type
CDC42EP5 p.Ala67Gly Uncertain significance ★ ⚠ same type
CDC42EP5 p.Ala67Thr 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/cdc42ep5-p-pro77ser (accessed [today's date]).

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