Is CDC42EP4 p.Ser80Phe (c.239C>T) pathogenic?

CDC42EP4 p.Ser80Phe (c.239C>T) is classified Uncertain significance in CDC42EP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). AlphaMissense: likely pathogenic (0.5668); Absent from gnomAD v4.1.

How common is CDC42EP4 p.Ser80Phe (c.239C>T) in the general population?

CDC42EP4 p.Ser80Phe (c.239C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42EP4 p.Ser80Phe (c.239C>T)?

AlphaMissense predicts likely pathogenic (score 0.5668) — an in-silico prediction, not a clinical call.

CDC42EP4 p.Ser80Phe

c.239C>T · VCV4650894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5668 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5668	likely pathogenic
REVEL	0.641	indeterminate
SaProt	LLR -7.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.57, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,067 bp · p 0.41 · regional, not allelic
Overall
CADD	28.3	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

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: CDC42EP4
Protein: p.Ser80Phe
Coding: c.239C>T
MANE Select: NM_012121
Type: single nucleotide variant
Location: chr17:73286262 (GRCh38)
Gene constraint: LOEUF 1.577 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.67
Residue 80: the 'disordered' region

Full CDC42EP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC42EP4 p.Ala127Ser Uncertain significance ★ ⚠ same type
CDC42EP4 p.Ala128Thr Uncertain significance ★ ⚠ same type
CDC42EP4 p.Ala128Val Uncertain significance ★ ⚠ same type
CDC42EP4 p.Ala157Val Uncertain significance ★ ⚠ same type
CDC42EP4 p.Ala170Val Uncertain significance ★ ⚠ same type
CDC42EP4 p.Ala183Gly Uncertain significance ★ ⚠ same type
CDC42EP4 p.Ala203Val Uncertain significance ★ ⚠ same type
CDC42EP4 p.Ala252Val 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/cdc42ep4-p-ser80phe (accessed [today's date]).

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