EDN3 p.Val162=
c.486G>A · VCV3730416
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00801%, afr)
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 -1.1 | GERP -3.9 |
| Overall | ||
| CADD | 0.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00801%
African / African-American · 6/74,942 alleles
Filtering AF
0.00347%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00228%
Overall
0.000681%
11/1,614,126 alleles · very rare
exomes 6/1,461,890 · genomes 5/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00801% | 12,490 |
| Admixed American | 0.00667% | 15,002 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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.Val162=
- Coding
- c.486G>A
- MANE Select
- NM_207034
- Type
- single nucleotide variant
- Location
- chr20:59321137 (GRCh38)
- Gene constraint
- LOEUF 0.696 · pLI 0.38 (gnomAD)
- Structure
- AlphaFold pLDDT 56.84 · 1 PDB
- Residue 162
- the 'endothelin-like' region
Similar variants
- 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
- EDN3 p.Arg230Pro 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-val162 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown