CDH18 p.Ser194=
c.582C>T · rs147239335 · VCV781850
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.91%, 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 -6.1 | GERP -5.4 |
| Overall | ||
| CADD | 5.154 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.91%
Middle Eastern · 236/6,042 alleles
Filtering AF
3.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.34%
Overall
0.2%
3,217/1,610,188 alleles · low-frequency
exomes 2,926/1,457,924 · genomes 291/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 3.91% | 26 |
| Ashkenazi Jewishnot grpmax-eligible | 2.1% | 48 |
| Amishnot grpmax-eligible | 1.21% | 83 |
| South Asian | 0.747% | 134 |
| Remaining individualsnot grpmax-eligible | 0.442% | 226 |
| Admixed American | 0.345% | 290 |
| European (non-Finnish) | 0.097% | 1,031 |
| African / African-American | 0.0573% | 1,744 |
| Finnishnot grpmax-eligible | 0.00783% | 12,772 |
| East Asian | 0.00223% | 44,842 |
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.Ser194=
- Coding
- c.582C>T
- MANE Select
- NM_004934
- dbSNP
- rs147239335
- Type
- single nucleotide variant
- Location
- chr5:19721408 (GRCh38)
- Gene constraint
- LOEUF 0.737 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.57
- Residue 194
- the cadherin 2 domain
Similar variants
- CDH18 p.Pro386= 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-ser194 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown