Is BMPR2 p.Ser64Ter (c.189dup) pathogenic?

BMPR2 p.Ser64Ter (c.189dup) is classified Pathogenic in BMPR2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-04-13). Absent from gnomAD; Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Ser64Ter (c.189dup)?

BMPR2 p.Ser64Ter (c.189dup) is associated with Primary pulmonary hypertension, pulmonary arterial hypertension (ClinVar).

How common is BMPR2 p.Ser64Ter (c.189dup) in the general population?

BMPR2 p.Ser64Ter (c.189dup) is absent from gnomAD (gnomAD).

BMPR2 p.Ser64Ter

c.189dup · rs2469639019 · VCV1706632

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

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	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.7, 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.Ser64Ter
Coding: c.189dup
MANE Select: NM_001204
dbSNP: rs2469639019
Type: Duplication
Location: chr2:202464920 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 64: a disulfide bond; a UniProt-annotated variant site (in pph1; uncertain significance; unchanged subcellular localization)

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.Asn583fs Pathogenic/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

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-ser64ter (accessed [today's date]).

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