Is BMPR2 p.Arg303Cys (c.907C>T) pathogenic?

BMPR2 p.Arg303Cys (c.907C>T) is classified Uncertain significance in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). AlphaMissense: likely benign (0.177); Very rare (popmax 0.0022%, sas); Associated with pulmonary hypertension, primary, 1.

What condition is associated with BMPR2 p.Arg303Cys (c.907C>T)?

BMPR2 p.Arg303Cys (c.907C>T) is associated with pulmonary hypertension, primary, 1, pulmonary venoocclusive disease 1 (ClinVar).

How common is BMPR2 p.Arg303Cys (c.907C>T) in the general population?

BMPR2 p.Arg303Cys (c.907C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BMPR2 p.Arg303Cys (c.907C>T)?

AlphaMissense predicts likely benign (score 0.177) — an in-silico prediction, not a clinical call.

BMPR2 p.Arg303Cys

c.907C>T · VCV3585267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.177 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

pulmonary hypertension, primary, 1

Computational evidence

Protein change
AlphaMissense	0.177	likely benign
REVEL	0.582	indeterminate
SaProt	LLR -11.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 153 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,048 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000434% 7/1,613,270 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,524
Remaining individualsnot grpmax-eligible	0.0016%	62,472
Finnishnot grpmax-eligible	0.00157%	63,798
European (non-Finnish)	0.000254%	393,303

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.Arg303Cys
Coding: c.907C>T
MANE Select: NM_001204
Type: single nucleotide variant
Location: chr2:202520141 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 303: 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); an α-helix

Full BMPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pulmonary hypertension, primary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pulmonary venoocclusive disease 1

Similar variants

BMPR2 p.Arg303His Likely pathogenic ★★★ ⚠ same residue
BMPR2 p.Arg303Gly Uncertain significance ★ same residue
BMPR2 p.Arg303= 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

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-arg303cys (accessed [today's date]).

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