EDN3 p.Ser75=
c.225C>T · rs565731779 · VCV764644
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0253%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -4.9 |
| Overall | ||
| CADD | 2.132 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0253%
African / African-American · 19/75,044 alleles
Filtering AF
0.0165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00155%
25/1,613,892 alleles · ultra-rare
exomes 10/1,461,582 · genomes 15/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0253% | 3,950 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,832 |
| Admixed American | 0.00333% | 30,009 |
| European (non-Finnish) | 8.47e-05% | 1,179,942 |
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
- EDN3
- Protein
- p.Ser75=
- Coding
- c.225C>T
- MANE Select
- NM_207034
- dbSNP
- rs565731779
- Type
- single nucleotide variant
- Location
- chr20:59301582 (GRCh38)
- Gene constraint
- LOEUF 0.696 · pLI 0.38 (gnomAD)
- Structure
- AlphaFold pLDDT 56.84 · 1 PDB
- Residue 75
- the 'disordered' region
Similar variants
- EDN3 p.Ser75Asn Uncertain significance ★ ⚠ same residue
- EDN3 c.-19C>A Uncertain significance ★★ same type
- EDN3 c.-86G>A Uncertain significance ★★ same type
- EDN3 p.Arg137Gln Uncertain significance ★★ same type
- EDN3 p.Arg154Gln Uncertain significance ★★ ⚠ same type
- EDN3 p.Arg158Ser Uncertain significance ★★ ⚠ same type
- EDN3 p.Arg230Cys Uncertain significance ★★ ⚠ same type
- EDN3 p.Arg230His 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/edn3-p-ser75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown