Is CDC42EP2 p.Phe83Leu (c.249C>G) pathogenic?

CDC42EP2 p.Phe83Leu (c.249C>G) is classified Uncertain significance in CDC42EP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). AlphaMissense: likely pathogenic (0.8328); Ultra-rare (popmax 0.0329%, mid).

How common is CDC42EP2 p.Phe83Leu (c.249C>G) in the general population?

CDC42EP2 p.Phe83Leu (c.249C>G) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CDC42EP2 p.Phe83Leu (c.249C>G)?

AlphaMissense predicts likely pathogenic (score 0.8328) — an in-silico prediction, not a clinical call.

CDC42EP2 p.Phe83Leu

c.249C>G · rs764266704 · VCV2483422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8328 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8328	likely pathogenic
REVEL	0.363	indeterminate
SaProt	LLR -4.72	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 3.3	GERP -0.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 629 bp · p 0.06 · regional, not allelic
Overall
CADD	21.7	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

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00316% 51/1,614,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
South Asian	0.00439%	22,771
European (non-Finnish)	0.00373%	26,818
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Phe83Leu
Coding: c.249C>G
MANE Select: NM_006779
dbSNP: rs764266704
Type: single nucleotide variant
Location: chr11:65321147 (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-phe83leu (accessed [today's date]).

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