Is BMPR2 p.Arg584Ter (c.1750C>T) pathogenic?

BMPR2 p.Arg584Ter (c.1750C>T) is classified Pathogenic in BMPR2 (ClinVar, Single submitter, 3 submitters; last evaluated 2022-09-07). Very rare (popmax 0.00167%, amr); Associated with pulmonary venoocclusive disease 1.

What condition is associated with BMPR2 p.Arg584Ter (c.1750C>T)?

BMPR2 p.Arg584Ter (c.1750C>T) is associated with pulmonary venoocclusive disease 1, pulmonary arterial hypertension, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Arg584Ter (c.1750C>T) in the general population?

BMPR2 p.Arg584Ter (c.1750C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Pulmonary venoocclusive disease inherited?

Typically Autosomal recessive, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

BMPR2 p.Arg584Ter

c.1750C>T · rs765887545 · VCV425965

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

pulmonary venoocclusive disease 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.5, phastCons 0.98
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,976 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,990 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,976
African / African-American	0.00134%	74,890
European (non-Finnish)	0.000254%	393,345

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: BMPR2
Protein: p.Arg584Ter
Coding: c.1750C>T
MANE Select: NM_001204
dbSNP: rs765887545
Type: single nucleotide variant
Location: chr2:202555415 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 584: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); a UniProt-annotated variant site (in pph1; loss of localization to the plasma membrane; localized to the cytoplasm)

Full BMPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pulmonary venoocclusive disease 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pulmonary arterial hypertension pulmonary hypertension, primary, 1

For Pulmonary venoocclusive disease (Orphanet):

Inheritance: Autosomal recessive, Not applicable
Onset: All ages
Prevalence: <1 / 1 000 000 (France)

Similar variants

BMPR2 p.Arg584Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BMPR2 p.Arg584Gln Uncertain significance ★ ⚠ same residue
BMPR2 c.1276+3A>G Likely pathogenic ★★★ same condition
BMPR2 c.1276+3A>T Likely pathogenic ★★★ same condition
BMPR2 c.1276+4A>G Likely pathogenic ★★★ same condition
BMPR2 c.1277-8A>G Pathogenic ★★★ same condition
BMPR2 c.1277-9A>G Pathogenic ★★★ same condition
BMPR2 c.1413+1G>A Pathogenic ★★★ same condition

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/bmpr2-p-arg584ter (accessed [today's date]).

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