CDH2 p.Ala816=
c.2448C>T · rs1041985 · VCV1253751
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 44.7%, amr) — too common for a highly-penetrant pathogenic allele
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 -13 | GERP -5.7 |
| Overall | ||
| CADD | 0.289 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
44.7%
Admixed American · 26,789/59,978 alleles
Filtering AF
44.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 44%
Overall
31.7%
510,881/1,612,960 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 44.7% | 2 |
| East Asian | 42.1% | 2 |
| South Asian | 37% | 3 |
| Finnishnot grpmax-eligible | 35.5% | 3 |
| Middle Eastern | 33.6% | 3 |
| Amishnot grpmax-eligible | 32.9% | 3 |
| Remaining individualsnot grpmax-eligible | 32.5% | 3 |
| European (non-Finnish) | 30.9% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 30.5% | 3 |
| African / African-American | 17% | 6 |
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.Ala816=
- Coding
- c.2448C>T
- MANE Select
- NM_001792
- dbSNP
- rs1041985
- Type
- single nucleotide variant
- Location
- chr18:27963423 (GRCh38)
- Gene constraint
- LOEUF 0.336 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.68
Similar variants
- CDH2 p.Ala816Thr 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-ala816 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown