CDH12 p.Leu222=
c.666G>A · rs563179062 · VCV757730
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, 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 2.2 | GERP -0.38, phastCons 1 |
| Overall | ||
| CADD | 11.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,872 alleles
Filtering AF
0.000879%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000719%
Overall
0.00124%
20/1,610,374 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,436 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,344 |
| European (non-Finnish) | 0.00144% | 69,298 |
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.Leu222=
- Coding
- c.666G>A
- MANE Select
- NM_004061
- dbSNP
- rs563179062
- Type
- single nucleotide variant
- Location
- chr5:21842309 (GRCh38)
- Gene constraint
- LOEUF 0.668 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.19
- Residue 222
- the cadherin 2 domain
Similar variants
- 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
- CDH12 p.Pro213= 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-leu222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown