Is CDC42EP3 p.Phe53Ser (c.158T>C) pathogenic?

CDC42EP3 p.Phe53Ser (c.158T>C) is classified Uncertain significance in CDC42EP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely pathogenic (0.9982); Very rare (popmax 8.47e-05%, nfe); Associated with CDC42EP3-related condition.

What condition is associated with CDC42EP3 p.Phe53Ser (c.158T>C)?

CDC42EP3 p.Phe53Ser (c.158T>C) is associated with CDC42EP3-related condition (ClinVar).

How common is CDC42EP3 p.Phe53Ser (c.158T>C) in the general population?

CDC42EP3 p.Phe53Ser (c.158T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CDC42EP3 p.Phe53Ser (c.158T>C)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

CDC42EP3 p.Phe53Ser

c.158T>C · VCV3349806

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CDC42EP3-related condition

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic · top 1% in CDC42EP3
REVEL	0.938	strongly pathogenic-leaning
SaProt	LLR -10.39	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 761 bp · p 0.9 · regional, not allelic
Overall
CADD	29.0	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.84e-05% 1/1,461,884 alleles · very rare

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: CDC42EP3
Protein: p.Phe53Ser
Coding: c.158T>C
MANE Select: NM_006449
Type: single nucleotide variant
Location: chr2:37646430 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 58.43

Full CDC42EP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDC42EP3-related condition

Similar variants

CDC42EP3 p.Lys46Arg Uncertain significance ★★ ⚠ same type
CDC42EP3 p.Asn62Ser Uncertain significance ★ ⚠ same type
CDC42EP3 p.Asn88Lys Uncertain significance ★ ⚠ same type
CDC42EP3 p.Asp198Asn Uncertain significance ★ ⚠ same type
CDC42EP3 p.Asp92Tyr Uncertain significance ★ ⚠ same type
CDC42EP3 p.Cys145Trp Uncertain significance ★ ⚠ same type
CDC42EP3 p.Gln154Leu Uncertain significance ★ ⚠ same type
CDC42EP3 p.Gln77His 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/cdc42ep3-p-phe53ser (accessed [today's date]).

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