Is BMPR2 p.Lys512fs (c.1536del) pathogenic?

BMPR2 p.Lys512fs (c.1536del) is classified Pathogenic in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-25). Absent from gnomAD; Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Lys512fs (c.1536del)?

BMPR2 p.Lys512fs (c.1536del) is associated with Primary pulmonary hypertension (ClinVar).

How common is BMPR2 p.Lys512fs (c.1536del) in the general population?

BMPR2 p.Lys512fs (c.1536del) is absent from gnomAD (gnomAD).

BMPR2 p.Lys512fs

c.1536del · rs1574505369 · VCV660183

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 11 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BMPR2
Protein: p.Lys512fs
Coding: c.1536del
MANE Select: NM_001204
dbSNP: rs1574505369
Type: Deletion
Location: chr2:202552836 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 512: 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); a UniProt-annotated variant site (in pph1; no effect on localization to the cell surface; no effect on bmp4 binding; when transfected in epithelial cells it results in constitutive p38mapk phosphorylation consistent with a gain of function in the activation of p38mapk cascade)

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

Similar variants

BMPR2 p.Asn861fs Pathogenic ★★ same condition
BMPR2 p.Pro366fs Pathogenic ★★ same condition
BMPR2 p.Pro739fs Pathogenic ★★ same condition
BMPR2 p.Lys512Arg Uncertain significance ★★ ⚠ same residue
BMPR2 c.1125_1128+16del Pathogenic ★ same condition
BMPR2 p.Arg321fs Pathogenic ★ same condition
BMPR2 p.Arg357fs Pathogenic ★ same condition
BMPR2 p.Arg535fs 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-lys512fs (accessed [today's date]).

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