CDH2 p.Leu15=
c.43C>T · rs558600173 · VCV1631334
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0851%, 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 4.5 | GERP 0.79, phastCons 1 |
| Overall | ||
| CADD | 12.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0851%
European (non-Finnish) · 931/1,093,884 alleles
Filtering AF
0.0805%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0787%
Overall
0.072%
1,035/1,437,052 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0851% | 1,175 |
| Remaining individualsnot grpmax-eligible | 0.0768% | 1,302 |
| South Asian | 0.0439% | 2,277 |
| Finnishnot grpmax-eligible | 0.0265% | 3,775 |
| Middle Eastern | 0.025% | 4,006 |
| African / African-American | 0.0177% | 5,659 |
| Admixed American | 0.0142% | 7,065 |
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.Leu15=
- Coding
- c.43C>T
- MANE Select
- NM_001792
- dbSNP
- rs558600173
- Type
- single nucleotide variant
- Location
- chr18:28176980 (GRCh38)
- Gene constraint
- LOEUF 0.336 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.68
Similar variants
- CDH2 p.Leu15Val 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-leu15 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown