Is EDNRB p.Pro72Ser (c.214C>T) pathogenic?

EDNRB p.Pro72Ser (c.214C>T) is classified Uncertain significance in EDNRB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-12). AlphaMissense: likely benign (0.0751); Ultra-rare (popmax 0.0267%, afr).

How common is EDNRB p.Pro72Ser (c.214C>T) in the general population?

EDNRB p.Pro72Ser (c.214C>T) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about EDNRB p.Pro72Ser (c.214C>T)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

EDNRB p.Pro72Ser

c.214C>T · rs150750272 · VCV2185276

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -1.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 20 kb · p 8.1e-06 · regional, not allelic
Overall
CADD	14.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0267% African / African-American · 20/74,814 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00149% 24/1,611,906 alleles · ultra-rare exomes 12/1,459,924 · genomes 12/151,982 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,741
Admixed American	0.00334%	29,957
South Asian	0.0011%	91,016
European (non-Finnish)	8.48e-05%	1,178,555

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: EDNRB
Protein: p.Pro72Ser
Coding: c.214C>T
MANE Select: NM_001122659
dbSNP: rs150750272
Type: single nucleotide variant
Location: chr13:77918360 (GRCh38)
Gene constraint: LOEUF 0.585 · pLI 0.49 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 75.37 · 18 PDB
Residue 72: the 'disordered' region

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

Similar variants

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
EDNRB p.Arg201Pro 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-pro72ser (accessed [today's date]).

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