CDH12 p.Ala616=
c.1848G>A · rs139945013 · VCV741395
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0694%, afr)
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 0.98 | GERP -3.8, phastCons 0.017 |
| Overall | ||
| CADD | 10.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0694%
African / African-American · 52/74,890 alleles
Filtering AF
0.0543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.049%
Overall
0.00991%
160/1,613,732 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0694% | 1,440 |
| Admixed American | 0.0167% | 5,997 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,413 |
| South Asian | 0.00769% | 13,011 |
| European (non-Finnish) | 0.00712% | 14,046 |
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
- CDH12
- Protein
- p.Ala616=
- Coding
- c.1848G>A
- MANE Select
- NM_004061
- dbSNP
- rs139945013
- Type
- single nucleotide variant
- Location
- chr5:21755628 (GRCh38)
- Gene constraint
- LOEUF 0.668 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.19
Similar variants
- CDH12 p.Ala616Val Uncertain significance ★ ⚠ same residue
- CDH12 c.1003-3C>T Benign ★★ same type
- CDH12 p.Asp780= Likely benign ★★ same type
- CDH12 p.Gln60= Benign ★★ same type
- CDH12 p.Glu349Asp Benign ★★ ⚠ same type
- CDH12 p.Glu34Gln Benign ★★ same type
- CDH12 p.Ile475Thr Benign ★★ ⚠ same type
- CDH12 p.Ile598= Likely benign ★★ 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/cdh12-p-ala616 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown