CDH2 c.172+6A>C
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.78%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +6 | donor splice region (+6, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -4.5 |
| Non-coding constraint | Z -0.21 | 1 kb window · o/e 1.02 · regional · uncalibrated |
| Overall | ||
| CADD | 5.014 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.78%
African / African-American · 570/73,036 alleles
Filtering AF
0.727%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.706%
Overall
0.0455%
695/1,528,468 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.78% | 128 |
| Admixed American | 0.136% | 736 |
| Remaining individualsnot grpmax-eligible | 0.0605% | 1,654 |
| Middle Eastern | 0.034% | 2,940 |
| South Asian | 0.00344% | 29,109 |
| European (non-Finnish) | 0.000452% | 221,379 |
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.172+6A>C
- MANE Select
- NM_001792
- dbSNP
- rs188251941
- Type
- single nucleotide variant
- Location
- chr18:28147667 (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-172-plus-6a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown