CDH3 p.Ser559=
c.1677C>T · rs113689956 · VCV1142732
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, 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 -0.66 | GERP -2.5, phastCons 0.008 |
| Overall | ||
| CADD | 8.347 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.022%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0187%
Overall
0.00316%
51/1,614,166 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| African / African-American | 0.032% | 3,127 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,946 |
| Admixed American | 0.00333% | 30,011 |
| European (non-Finnish) | 0.00119% | 84,286 |
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.Ser559=
- Coding
- c.1677C>T
- MANE Select
- NM_004933 · reported on NM_001793
- dbSNP
- rs113689956
- Type
- single nucleotide variant
- Location
- chr16:68687618 (GRCh38)
- Structure
- AlphaFold pLDDT 78.70
- Residue 559
- the cadherin 5 domain
Similar variants
- CDH3 p.Ser559fs Pathogenic ★ same residue
- 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
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-ser559 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown