Is BMPR2 p.Asn583fs (c.1748dup) pathogenic?

BMPR2 p.Asn583fs (c.1748dup) is classified Pathogenic/Likely pathogenic in BMPR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-25). Very rare (popmax 0.0011%, sas); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Asn583fs (c.1748dup)?

BMPR2 p.Asn583fs (c.1748dup) is associated with Primary pulmonary hypertension, pulmonary arterial hypertension (ClinVar).

How common is BMPR2 p.Asn583fs (c.1748dup) in the general population?

BMPR2 p.Asn583fs (c.1748dup) is very rare (popmax 0.0011%, sas) (gnomAD).

BMPR2 p.Asn583fs

c.1748dup · rs772920507 · VCV1069660

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Primary pulmonary 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 12	GERP 2.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Overall 0.000137% 2/1,461,816 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,066
European (non-Finnish)	8.47e-05%	1,179,970

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.Asn583fs
Coding: c.1748dup
MANE Select: NM_001204
dbSNP: rs772920507
Type: Duplication
Location: chr2:202555406 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 583: 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

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

Also linked: pulmonary arterial hypertension

Similar variants

BMPR2 c.529+2dup Likely pathogenic ★★★ same condition
BMPR2 p.Gly63fs Pathogenic ★★ same condition
BMPR2 p.Arg381fs Pathogenic ★ same condition
BMPR2 p.Asn343fs Pathogenic ★ same condition
BMPR2 p.Gln692fs Likely pathogenic ★ same condition
BMPR2 p.Glu48fs Pathogenic ★ same condition
BMPR2 p.His324fs Pathogenic ★ same condition
BMPR2 p.His87fs 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-asn583fs (accessed [today's date]).

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