CDH15 p.Pro373=
c.1119C>T · rs570306656 · VCV747497
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0634%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.32 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.2 | GERP -2.8 |
| Overall | ||
| CADD | 13.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0634%
Admixed American · 38/59,978 alleles
Filtering AF
0.0474%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0418%
Overall
0.0036%
58/1,612,852 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0634% | 1,578 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,206 |
| African / African-American | 0.00666% | 15,013 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,570 |
| South Asian | 0.0011% | 90,978 |
| European (non-Finnish) | 8.47e-05% | 1,179,967 |
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
- CDH15
- Protein
- p.Pro373=
- Coding
- c.1119C>T
- MANE Select
- NM_004933
- dbSNP
- rs570306656
- Type
- single nucleotide variant
- Location
- chr16:89190383 (GRCh38)
- Gene constraint
- LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.70
- Residue 373
- the cadherin 3 domain
Similar variants
- CDH3 p.Asp373Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
- CDH3 p.Asp373Tyr Uncertain significance ★ ⚠ 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
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/cdh15-p-pro373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown