Is EDNRB p.Arg201Pro (c.602G>C) pathogenic?

EDNRB p.Arg201Pro (c.602G>C) is classified Uncertain significance in EDNRB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-03). AlphaMissense: likely pathogenic (0.9982); Absent from gnomAD v4.1.

How common is EDNRB p.Arg201Pro (c.602G>C) in the general population?

EDNRB p.Arg201Pro (c.602G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDNRB p.Arg201Pro (c.602G>C)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

EDNRB p.Arg201Pro

c.602G>C · rs780841273 · VCV871880

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic · top 3% in EDNRB
REVEL	0.558	indeterminate
SaProt	LLR -14.89	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 20 kb · p 8.1e-06 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: EDNRB
Protein: p.Arg201Pro
Coding: c.602G>C
MANE Select: NM_001122659
dbSNP: rs780841273
Type: single nucleotide variant
Location: chr13:77903355 (GRCh38)
Gene constraint: LOEUF 0.585 · pLI 0.49 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 75.37 · 18 PDB
Residue 201: an α-helix

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

Similar variants

EDNRB p.Arg201= Likely benign ★ same residue
EDNRB c.1085+1G>A Likely pathogenic ★★ same type
EDNRB c.596+1G>A Pathogenic/Likely pathogenic ★★ same type
EDNRB c.802-1G>A Likely pathogenic ★★ same type
EDNRB p.Arg253Ter Pathogenic ★★ same type
EDNRB c.*1412C>T Uncertain significance ★★ same type
EDNRB p.Ala310Thr Uncertain significance ★★ same type
EDNRB p.Arg124Lys 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/ednrb-p-arg201pro (accessed [today's date]).

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