CDH18 p.Pro386=
c.1158T>G · rs78589740 · VCV767995
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.75%, mid)
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 0.39 | GERP -4, phastCons 0.67 |
| Overall | ||
| CADD | 5.898 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.75%
Middle Eastern · 288/6,062 alleles
Filtering AF
4.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.12%
Overall
0.348%
5,622/1,613,816 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 4.75% | 21 |
| African / African-American | 2.71% | 37 |
| Ashkenazi Jewishnot grpmax-eligible | 2.13% | 47 |
| Amishnot grpmax-eligible | 1.21% | 83 |
| South Asian | 0.701% | 143 |
| Remaining individualsnot grpmax-eligible | 0.603% | 166 |
| Admixed American | 0.54% | 185 |
| European (non-Finnish) | 0.112% | 897 |
| Finnishnot grpmax-eligible | 0.0109% | 9,147 |
| East Asian | 0.00223% | 44,848 |
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
- CDH18
- Protein
- p.Pro386=
- Coding
- c.1158T>G
- MANE Select
- NM_004934
- dbSNP
- rs78589740
- Type
- single nucleotide variant
- Location
- chr5:19571674 (GRCh38)
- Gene constraint
- LOEUF 0.737 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.57
- Residue 386
- the cadherin 4 domain
Similar variants
- CDH18 p.Ser194= Benign ★★ same type
- CDH18 p.Ala435Thr Uncertain significance ★ ⚠ same type
- CDH18 p.Ala518Asp Uncertain significance ★ same type
- CDH18 p.Ala602Thr Uncertain significance ★ ⚠ same type
- CDH18 p.Ala609Pro Uncertain significance ★ same type
- CDH18 p.Ala615Gly Uncertain significance ★ ⚠ same type
- CDH18 p.Ala618Thr Uncertain significance ★ ⚠ same type
- CDH18 p.Ala682Pro 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/cdh18-p-pro386 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown