CDH5 p.Leu8=
c.24C>T · VCV3830200
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00678%, nfe)
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 -0.57 | GERP -3.5 |
| Overall | ||
| CADD | 2.185 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00678%
European (non-Finnish) · 80/1,179,376 alleles
Filtering AF
0.00555%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.00552%
89/1,612,710 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00678% | 14,742 |
| African / African-American | 0.00533% | 18,759 |
| East Asian | 0.00223% | 44,840 |
| Admixed American | 0.00167% | 60,000 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,416 |
| Finnishnot grpmax-eligible | 0.00156% | 63,978 |
| South Asian | 0.0011% | 90,988 |
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.Leu8=
- Coding
- c.24C>T
- MANE Select
- NM_001795
- Type
- single nucleotide variant
- Location
- chr16:66379361 (GRCh38)
- Gene constraint
- LOEUF 0.661 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.46
Similar variants
- CDH5 p.Val266= Benign ★★ same type
- 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
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-leu8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown