Is BMPR2 p.Asp669fs (c.2004del) pathogenic?

BMPR2 p.Asp669fs (c.2004del) is classified Likely pathogenic in BMPR2 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 6.84e-05%); Associated with pulmonary arterial hypertension.

What condition is associated with BMPR2 p.Asp669fs (c.2004del)?

BMPR2 p.Asp669fs (c.2004del) is associated with pulmonary arterial hypertension (ClinVar).

How common is BMPR2 p.Asp669fs (c.2004del) in the general population?

BMPR2 p.Asp669fs (c.2004del) is very rare (popmax 6.84e-05%) (gnomAD).

BMPR2 p.Asp669fs

Q: How is Idiopathic/heritable pulmonary arterial hypertension inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2004del · rs1574506781 · VCV812837

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

pulmonary arterial hypertension

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,808 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.Asp669fs
Coding: c.2004del
MANE Select: NM_001204
dbSNP: rs1574506781
Type: Deletion
Location: chr2:202555669 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 669: 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 arterial hypertension — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Idiopathic/heritable pulmonary arterial hypertension (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

BMPR2 c.247+1_247+7del Likely pathogenic ★★★ same condition
BMPR2 c.247+2del Likely pathogenic ★★★ same condition
BMPR2 c.419-38del Benign ★★★ same condition
BMPR2 p.Asn861fs Pathogenic ★★ same condition
BMPR2 p.Gly390fs Pathogenic/Likely pathogenic ★★ same condition
BMPR2 p.Pro739fs Pathogenic ★★ same condition
BMPR2 p.Asn817fs Pathogenic ★ same condition
BMPR2 p.Gln92fs 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-asp669fs (accessed [today's date]).

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