Is BMPR2 p.Val784= (c.2352C>T) pathogenic?

BMPR2 p.Val784= (c.2352C>T) is classified Uncertain significance in BMPR2 (ClinVar, Expert panel, 4 submitters; last evaluated 2026-04-10). Very rare (popmax 0.00602%, nfe); Associated with pulmonary arterial hypertension.

What condition is associated with BMPR2 p.Val784= (c.2352C>T)?

BMPR2 p.Val784= (c.2352C>T) is associated with pulmonary arterial hypertension, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Val784= (c.2352C>T) in the general population?

BMPR2 p.Val784= (c.2352C>T) is very rare (popmax 0.00602%, nfe) (gnomAD).

BMPR2 p.Val784=

Q: How is Idiopathic/heritable pulmonary arterial hypertension inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2352C>T · rs767560978 · VCV333647

Uncertain significance Expert panel

Classification

Uncertain significance

ClinVar

Review

Expert panel ★★★☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Conditions

pulmonary arterial hypertension

ClinGen expert panel — Pulmonary Hypertension VCEP

Uncertain Significance for pulmonary arterial hypertension. Applied ACMG criteria (verbatim):

PM2_Supporting BP7 BP4

Curation rationale (ClinGen, verbatim)

The NM_001204.7(BMPR2) c.2352C>T variant is a synonymous (silent) variant (p.Val784=). This variant is present in gnomADv2.1.1 controls at a frequency of 0.00002 and gnomADv4.1 at 0.00006 (PM2_supporting). In silico prediction algorithms indicate that the nucleotide is not highly conserved (REVEL score not available; CADD = 1.4; phyloP = 0.207) (BP4) and has no impact on splicing (SpliceAI = 0) (BP7). In summary, this variant is classified as a variant of uncertain significance for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BP4, BP7, PM2_supporting. (VCEP specifications version 2.0, 1/30/2026)

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.023, phastCons 1
Overall
CADD	6.953	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00602% European (non-Finnish) · 71/1,180,018 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00477% 77/1,614,008 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,620
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Finnishnot grpmax-eligible	0.00312%	32,014
African / African-American	0.00133%	74,908
South Asian	0.0011%	91,082

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.Val784=
Coding: c.2352C>T
MANE Select: NM_001204
dbSNP: rs767560978
Type: single nucleotide variant
Location: chr2:202556017 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 784: 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

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

Also linked: pulmonary hypertension, primary, 1

For Idiopathic/heritable pulmonary arterial hypertension (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

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
BMPR2 c.247+1G>A Likely pathogenic ★★★ same condition
BMPR2 c.247+5G>A Likely 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-val784 (accessed [today's date]).

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