Is BMPR2 p.Gln450Ter (c.1348C>T) pathogenic?

BMPR2 p.Gln450Ter (c.1348C>T) is classified Pathogenic in BMPR2 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-04-28). Absent from gnomAD v4.1; Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Gln450Ter (c.1348C>T)?

BMPR2 p.Gln450Ter (c.1348C>T) is associated with Primary pulmonary hypertension, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Gln450Ter (c.1348C>T) in the general population?

BMPR2 p.Gln450Ter (c.1348C>T) is absent from gnomAD v4.1 (gnomAD).

BMPR2 p.Gln450Ter

c.1348C>T · rs868369541 · VCV425927

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMPR2
Protein: p.Gln450Ter
Coding: c.1348C>T
MANE Select: NM_001204
dbSNP: rs868369541
Type: single nucleotide variant
Location: chr2:202542382 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 450: an α-helix; a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); the protein kinase domain; 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 hypertension, primary, 1

Similar variants

BMPR2 p.Gln450Arg Uncertain significance ★ ⚠ same residue
BMPR2 p.Gln450= Likely benign ★ same residue
BMPR2 c.1276+3A>G Likely pathogenic ★★★ same condition
BMPR2 c.1276+3A>T Likely pathogenic ★★★ same condition
BMPR2 c.1276+4A>G Likely pathogenic ★★★ same condition
BMPR2 c.1277-8A>G Pathogenic ★★★ same condition
BMPR2 c.1277-9A>G Pathogenic ★★★ same condition
BMPR2 c.1413+1G>A 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-gln450ter (accessed [today's date]).

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