CDH5 p.Val266=
c.798C>T · rs140545178 · VCV784343
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.554%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.59 | GERP -4 |
| Overall | ||
| CADD | 2.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.554%
African / African-American · 416/75,034 alleles
Filtering AF
0.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.493%
Overall
0.0367%
592/1,613,392 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.554% | 180 |
| Remaining individualsnot grpmax-eligible | 0.0544% | 1,838 |
| Middle Eastern | 0.033% | 3,029 |
| Admixed American | 0.0234% | 4,282 |
| South Asian | 0.0187% | 5,348 |
| European (non-Finnish) | 0.00916% | 10,922 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,566 |
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
- CDH5
- Protein
- p.Val266=
- Coding
- c.798C>T
- MANE Select
- NM_001795
- dbSNP
- rs140545178
- Type
- single nucleotide variant
- Location
- chr16:66390419 (GRCh38)
- Gene constraint
- LOEUF 0.661 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.46
- Residue 266
- the cadherin 3 domain
Similar variants
- CDH5 p.Ala13Ser Uncertain significance ★ ⚠ same type
- CDH5 p.Ala187Val Uncertain significance ★ ⚠ same type
- CDH5 p.Ala201Ser Uncertain significance ★ ⚠ same type
- CDH5 p.Ala21Thr Uncertain significance ★ ⚠ same type
- CDH5 p.Ala229Val Uncertain significance ★ ⚠ same type
- CDH5 p.Ala353Val Uncertain significance ★ ⚠ same type
- CDH5 p.Ala395Thr Uncertain significance ★ ⚠ same type
- CDH5 p.Ala603Pro 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/cdh5-p-val266 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown