Is BMPR2 p.Glu661del (c.1977AGA[2]) pathogenic?

BMPR2 p.Glu661del (c.1977AGA[2]) is classified Uncertain significance in BMPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-07). Very rare (popmax 8.47e-05%, nfe); Associated with pulmonary hypertension, primary, 1.

What condition is associated with BMPR2 p.Glu661del (c.1977AGA[2])?

BMPR2 p.Glu661del (c.1977AGA[2]) is associated with pulmonary hypertension, primary, 1, pulmonary venoocclusive disease 1 (ClinVar).

How common is BMPR2 p.Glu661del (c.1977AGA[2]) in the general population?

BMPR2 p.Glu661del (c.1977AGA[2]) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

BMPR2 p.Glu661del

c.1977AGA[2] · VCV3585293

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

pulmonary hypertension, primary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.84e-05% 1/1,461,834 alleles · very rare

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.Glu661del
Coding: c.1977AGA[2]
MANE Select: NM_001204
Type: Microsatellite
Location: chr2:202555642 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 661: 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 hypertension, primary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pulmonary venoocclusive disease 1

Similar variants

BMPR2 p.Glu661Ter Pathogenic same residue
BMPR2 c.1587-7_1587-4del Likely benign ★★★ same condition
BMPR2 p.Ser52_His53insTer Pathogenic/Likely pathogenic ★★ same condition
BMPR2 p.Glu661Gln Uncertain significance ★★ ⚠ same residue
BMPR2 p.Arg266fs Pathogenic ★ same condition
BMPR2 p.Arg459fs Pathogenic ★ same condition
BMPR2 p.Leu293fs Likely pathogenic ★ same condition
BMPR2 c.418+5_418+8del 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-glu661del (accessed [today's date]).

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