Is CDC42EP2 p.Pro73Ser (c.217C>T) pathogenic?

CDC42EP2 p.Pro73Ser (c.217C>T) is classified Uncertain significance in CDC42EP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.0721); Ultra-rare (popmax 0.011%, sas).

How common is CDC42EP2 p.Pro73Ser (c.217C>T) in the general population?

CDC42EP2 p.Pro73Ser (c.217C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about CDC42EP2 p.Pro73Ser (c.217C>T)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

CDC42EP2 p.Pro73Ser

c.217C>T · VCV3998598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -5.26	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 0.56	GERP -3.5, phastCons 0.002
Regional constraint	o/e 0.89	unconstrained · MANE · 629 bp · p 0.06 · regional, not allelic
Overall
CADD	1.272	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 0.011% South Asian · 10/91,086 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.000752% 11/1,461,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,109
European (non-Finnish)	8.47e-05%	1,180,006

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: CDC42EP2
Protein: p.Pro73Ser
Coding: c.217C>T
MANE Select: NM_006779
Type: single nucleotide variant
Location: chr11:65321115 (GRCh38)
Gene constraint: LOEUF 1.364 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 62.22

Full CDC42EP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC42EP2 p.Gly93= Benign ★★ same type
CDC42EP2 p.Ala89Thr Uncertain significance ★ ⚠ same type
CDC42EP2 p.Arg11Cys Uncertain significance ★ ⚠ same type
CDC42EP2 p.Arg132His Uncertain significance ★ ⚠ same type
CDC42EP2 p.Arg22Gln Uncertain significance ★ ⚠ same type
CDC42EP2 p.Arg38Cys Uncertain significance ★ ⚠ same type
CDC42EP2 p.Arg87Cys Uncertain significance ★ ⚠ same type
CDC42EP2 p.Arg87Pro 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/cdc42ep2-p-pro73ser (accessed [today's date]).

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