Is CDH2 p.Arg232= (c.696G>T) pathogenic?

CDH2 p.Arg232= (c.696G>T) is classified Benign/Likely benign in CDH2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.73%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDH2 p.Arg232= (c.696G>T)?

CDH2 p.Arg232= (c.696G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH2 p.Arg232= (c.696G>T) in the general population?

CDH2 p.Arg232= (c.696G>T) is low-frequency (popmax 1.73%, afr) (gnomAD).

CDH2 p.Arg232=

c.696G>T · rs520232 · VCV1601655

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.73%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3.4
Overall
CADD	6.372	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.73% African / African-American · 1,295/74,960 alleles

Filtering AF 1.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.62%

Overall 0.0883% 1,424/1,613,406 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.73%	58
Admixed American	0.0917%	1,090
Remaining individualsnot grpmax-eligible	0.0864%	1,157
Middle Eastern	0.067%	1,492
South Asian	0.0022%	45,490
European (non-Finnish)	0.00119%	84,267

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: CDH2
Protein: p.Arg232=
Coding: c.696G>T
MANE Select: NM_001792
dbSNP: rs520232
Type: single nucleotide variant
Location: chr18:28009723 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 232: the cadherin 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH2 p.Arg232Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH2 p.Arg232Gly Uncertain significance ★ ⚠ same residue
CDH2 p.Arg232Trp Uncertain significance ★ ⚠ same residue
CDH2 p.Ala21Val Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala294Gly Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala299Thr Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala415Ser Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala418Ser Uncertain significance ★★ ⚠ same condition

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-arg232 (accessed [today's date]).

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