CDH2 p.Ala512=
c.1536C>T · rs190071108 · VCV1641490
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.223%, eas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -5.6 |
| Overall | ||
| CADD | 6.306 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.223%
East Asian · 100/44,870 alleles
Filtering AF
0.187%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.174%
Overall
0.0128%
206/1,613,924 alleles · rare
exomes 179/1,461,684 · genomes 27/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.223% | 449 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,682 |
| European (non-Finnish) | 0.00712% | 14,046 |
| Admixed American | 0.00666% | 15,004 |
| African / African-American | 0.00666% | 15,005 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,600 |
| South Asian | 0.0011% | 91,072 |
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.Ala512=
- Coding
- c.1536C>T
- MANE Select
- NM_001792
- dbSNP
- rs190071108
- Type
- single nucleotide variant
- Location
- chr18:27990159 (GRCh38)
- Gene constraint
- LOEUF 0.336 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.68
- Residue 512
- the cadherin 4 domain
Similar variants
- CDH2 p.Ala512Val 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
- CDH2 p.Ala418Thr Uncertain significance ★★ ⚠ same condition
- CDH2 p.Ala610Thr 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-ala512 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown