Is EDN3 p.Pro61= (c.183T>C) pathogenic?

EDN3 p.Pro61= (c.183T>C) is classified Likely benign in EDN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-19). Absent from gnomAD v4.1.

How common is EDN3 p.Pro61= (c.183T>C) in the general population?

EDN3 p.Pro61= (c.183T>C) is absent from gnomAD v4.1 (gnomAD).

EDN3 p.Pro61=

c.183T>C · VCV3673745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -2.8	GERP -0.44
Overall
CADD	2.768	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EDN3
Protein: p.Pro61=
Coding: c.183T>C
MANE Select: NM_207034
Type: single nucleotide variant
Location: chr20:59301540 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI 0.38 (gnomAD)
Structure: AlphaFold pLDDT 56.84 · 1 PDB
Residue 61: the 'disordered' region

Full EDN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDN3 p.Pro61Leu 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-pro61 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown