CDH2 p.Ala21=
c.63G>A · rs17469238 · VCV1753318
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0145%, nfe)
Conditions
1
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 -5.9 | GERP -4.5 |
| Overall | ||
| CADD | 0.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0145%
European (non-Finnish) · 167/1,151,812 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0119%
Overall
0.0114%
178/1,567,856 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0145% | 6,897 |
| Remaining individualsnot grpmax-eligible | 0.00987% | 10,134 |
| East Asian | 0.00673% | 14,859 |
| South Asian | 0.00233% | 42,913 |
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.Ala21=
- Coding
- c.63G>A
- MANE Select
- NM_001792
- dbSNP
- rs17469238
- Type
- single nucleotide variant
- Location
- chr18:28147782 (GRCh38)
- Gene constraint
- LOEUF 0.336 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.68
- Residue 21
- a UniProt-annotated variant site (in)
Similar variants
- CDH2 p.Ala21Val Uncertain significance ★★ ⚠ same residue
- CDH2 p.Ala21Thr Benign/Likely benign ★★ same residue
- CDH2 p.Ala21Ser Uncertain significance ★ ⚠ same residue
- 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
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-ala21 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown