Is BMPR2 p.Ser140fs (c.418del) pathogenic?

BMPR2 p.Ser140fs (c.418del) is classified Pathogenic in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-30). Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Ser140fs (c.418del)?

BMPR2 p.Ser140fs (c.418del) is associated with Primary pulmonary hypertension (ClinVar).

BMPR2 p.Ser140fs

c.418del · VCV3661545

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.31	GERP -0.99, phastCons 0.99

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

Variant & gene context

Gene: BMPR2
Protein: p.Ser140fs
Coding: c.418del
MANE Select: NM_001204
Type: Deletion
Location: chr2:202467689 (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

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 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
BMPR2 p.Asn817fs 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-ser140fs (accessed [today's date]).

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