CDH3 p.Leu667=
c.2001G>C · rs201014182 · VCV1543714
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.129%, eas)
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 0.14 | GERP -4.4, phastCons 0.001 |
| Overall | ||
| CADD | 3.229 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.129%
East Asian · 58/44,844 alleles
Filtering AF
0.103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0931%
Overall
0.00416%
67/1,610,674 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.129% | 773 |
| South Asian | 0.00769% | 12,996 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,148 |
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
- CDH3
- Protein
- p.Leu667=
- Coding
- c.2001G>C
- MANE Select
- NM_001793
- dbSNP
- rs201014182
- Type
- single nucleotide variant
- Location
- chr16:68691925 (GRCh38)
- Gene constraint
- LOEUF 0.823 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.71 · 19 PDB
Similar variants
- CDH3 c.1796-2A>G Pathogenic ★★ same type
- CDH3 c.691+1G>A Pathogenic/Likely pathogenic ★★ same type
- CDH3 p.Arg103Ter Pathogenic ★★ same type
- CDH3 p.Arg221Ter Pathogenic ★★ same type
- CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same type
- CDH3 p.Gln299Ter Pathogenic ★★ same type
- CDH3 p.Glu708Ter Likely pathogenic ★★ same type
- CDH3 p.Trp362Ter Pathogenic ★★ 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/cdh3-p-leu667 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown