CDH15 p.Asp742=
c.2226C>T · rs370556933 · VCV2647046
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, 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 -9.3 | GERP -3.7 |
| Overall | ||
| CADD | 0.358 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,076 alleles
Filtering AF
0.00212%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00138%
Overall
0.000808%
13/1,608,298 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,076 |
| South Asian | 0.00554% | 18,059 |
| Admixed American | 0.00168% | 59,528 |
| Finnishnot grpmax-eligible | 0.00161% | 62,250 |
| African / African-American | 0.00134% | 74,790 |
| European (non-Finnish) | 0.00034% | 294,487 |
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.Asp742=
- Coding
- c.2226C>T
- MANE Select
- NM_004933
- dbSNP
- rs370556933
- Type
- single nucleotide variant
- Location
- chr16:89194936 (GRCh38)
- Gene constraint
- LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.70
Similar variants
- CDH15 p.Asp742His Uncertain significance ★ ⚠ same residue
- CDH15 p.Asp742Glu Likely benign ★ 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-asp742 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown