CDH2 p.Pro392Leu
c.1175C>T · VCV3697013
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
AlphaMissense
likely benign
0.1078 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1078 | likely benign |
|---|---|---|
| REVEL | 0.295 | indeterminate |
| SaProt | LLR -11.63 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.8, phastCons 1 |
| Regional constraint | o/e 0.78 | unconstrained · MANE · 27 kb · p 4e-09 · regional, not allelic |
| Overall | ||
| CADD | 25.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CDH2
- Protein
- p.Pro392Leu
- Coding
- c.1175C>T
- MANE Select
- NM_001792
- Type
- single nucleotide variant
- Location
- chr18:27992824 (GRCh38)
- Gene constraint
- LOEUF 0.336 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.68
- Residue 392
- the cadherin 3 domain
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-p-pro392leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown