CDH3 p.His186=
c.558C>T · rs775627086 · VCV761020
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -11 | GERP -4.4 |
| Overall | ||
| CADD | 0.477 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00815%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.0013%
21/1,614,040 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| African / African-American | 0.0147% | 6,810 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| East Asian | 0.00223% | 44,886 |
| Admixed American | 0.00167% | 59,998 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
| European (non-Finnish) | 0.000339% | 295,007 |
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.His186=
- Coding
- c.558C>T
- MANE Select
- NM_001793
- dbSNP
- rs775627086
- Type
- single nucleotide variant
- Location
- chr16:68678773 (GRCh38)
- Gene constraint
- LOEUF 0.823 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.71 · 19 PDB
- Residue 186
- a β-strand; the cadherin 1 domain
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-his186 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown