Is BMPR2 p.Glu195Ter (c.583G>T) pathogenic?

BMPR2 p.Glu195Ter (c.583G>T) is classified Pathogenic in BMPR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-07-01). Absent from gnomAD v4.1; Associated with pulmonary venoocclusive disease 1.

What condition is associated with BMPR2 p.Glu195Ter (c.583G>T)?

BMPR2 p.Glu195Ter (c.583G>T) is associated with pulmonary venoocclusive disease 1 (ClinVar).

How common is BMPR2 p.Glu195Ter (c.583G>T) in the general population?

BMPR2 p.Glu195Ter (c.583G>T) is absent from gnomAD v4.1 (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.Glu195Ter

c.583G>T · rs397514497 · VCV39423

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 5 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1, phastCons 1
Overall
CADD	42.0	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

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: BMPR2
Protein: p.Glu195Ter
Coding: c.583G>T
MANE Select: NM_001204
dbSNP: rs397514497
Type: single nucleotide variant
Location: chr2:202514941 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB

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

For Pulmonary venoocclusive disease (Orphanet):

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

Similar variants

BMPR2 c.1277-9A>G Pathogenic ★★★ same condition
BMPR2 c.529+1G>A Likely pathogenic ★★★ same condition
BMPR2 c.968-5A>G Pathogenic ★★★ same condition
BMPR2 p.Arg303His Likely pathogenic ★★★ ⚠ same condition
BMPR2 p.Arg491Gln Pathogenic ★★★ same condition
BMPR2 p.Cys347Tyr Likely pathogenic ★★★ same condition
BMPR2 p.Arg266Thr Uncertain significance ★★★ ⚠ same condition
BMPR2 p.Arg842Ser Uncertain significance ★★★ ⚠ 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-glu195ter (accessed [today's date]).

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