CDH2 c.60+18C>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00365%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +18 | near-intronic (+18 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP -0.23, phastCons 0.84 |
| Non-coding constraint | Z -0.45 | 1 kb window · o/e 1.03 · regional · uncalibrated |
| Overall | ||
| CADD | 13.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00365%
Admixed American · 1/27,398 alleles
Filtering AF
3.5e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.3e-05%
Overall
0.000283%
3/1,061,248 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00365% | 27,398 |
| European (non-Finnish) | 0.000211% | 473,276 |
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
- CDH2
- Coding
- c.60+18C>A
- MANE Select
- NM_001792
- dbSNP
- rs2144382166
- Type
- single nucleotide variant
- Location
- chr18:28176945 (GRCh38)
- Gene constraint
- LOEUF 0.336 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.68
Similar variants
- CDH2 c.1344+1G>A Pathogenic/Likely pathogenic ★★ same type
- CDH2 c.702+1G>A Pathogenic/Likely pathogenic ★★ same type
- CDH2 p.Tyr676Cys Pathogenic ★★ same type
- CDH2 c.61-1G>A Uncertain significance ★★ same type
- CDH2 c.848-16T>G Uncertain significance ★★ same type
- CDH2 p.Ala106Val Uncertain significance ★★ ⚠ same type
- CDH2 p.Ala21Val Uncertain significance ★★ ⚠ same type
- CDH2 p.Ala294Gly Uncertain significance ★★ ⚠ 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/cdh2-c-60-plus-18c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown