CDH2 p.Asp684=
c.2052T>C · rs777968729 · VCV2094289
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
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 1.4 | GERP -2.1, phastCons 1 |
| Overall | ||
| CADD | 6.194 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,080 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000274%
4/1,461,618 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,360 |
| European (non-Finnish) | 8.48e-05% | 1,179,796 |
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.Asp684=
- Coding
- c.2052T>C
- MANE Select
- NM_001792
- dbSNP
- rs777968729
- Type
- single nucleotide variant
- Location
- chr18:27985157 (GRCh38)
- Gene constraint
- LOEUF 0.336 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.68
- Residue 684
- the cadherin 5 domain
Similar variants
- CDH2 p.Asp684Tyr Uncertain significance ★ ⚠ same residue
- CDH2 c.1344+1G>A Pathogenic/Likely pathogenic ★★ same type
- CDH2 c.702+1G>A Pathogenic/Likely pathogenic ★★ same type
- CDH2 p.Tyr676Cys Pathogenic ★★ same type
- CDH2 c.61-1G>A Uncertain significance ★★ same type
- CDH2 c.848-16T>G Uncertain significance ★★ same type
- CDH2 p.Ala106Val Uncertain significance ★★ ⚠ same type
- CDH2 p.Ala21Val 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-asp684 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown