Is CDH2 p.Arg697Leu (c.2090_2091delinsTC) pathogenic?

CDH2 p.Arg697Leu (c.20902091delinsTC) is classified Uncertain significance in CDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-20). Absent from gnomAD.

How common is CDH2 p.Arg697Leu (c.2090_2091delinsTC) in the general population?

CDH2 p.Arg697Leu (c.2090_2091delinsTC) is absent from gnomAD (gnomAD).

CDH2 p.Arg697Leu

c.2090_2091delinsTC · rs2510792391 · VCV2419796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -9.1	GERP -5.6
Regional constraint	o/e 0.78	unconstrained · MANE · 27 kb · p 4e-09 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: CDH2
Protein: p.Arg697Leu
Coding: c.2090_2091delinsTC
MANE Select: NM_001792
dbSNP: rs2510792391
Type: Indel
Location: chr18:27985118 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 697: the cadherin 5 domain

Full CDH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH2 p.Arg697Cys Uncertain significance ★★ same residue
CDH2 p.Arg697= Benign ★★ same residue
CDH2 p.Arg697His Uncertain significance ★ same residue
CDH2 c.1021-21_1021-20delinsGA Uncertain significance ★ same type
CDH2 p.Arg3Trp Uncertain significance ★ same type
CDH2 p.Pro477Leu Uncertain significance ★ same type
CDH2 p.Thr111Met 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/cdh2-p-arg697leu (accessed [today's date]).

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