Is BMPR2 p.Arg899Gly (c.2695C>G) pathogenic?

BMPR2 p.Arg899Gly (c.2695C>G) is classified Likely benign in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: ambiguous (0.3466); Very rare (popmax 8.47e-05%, nfe); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Arg899Gly (c.2695C>G)?

BMPR2 p.Arg899Gly (c.2695C>G) is associated with Primary pulmonary hypertension (ClinVar).

How common is BMPR2 p.Arg899Gly (c.2695C>G) in the general population?

BMPR2 p.Arg899Gly (c.2695C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BMPR2 p.Arg899Gly (c.2695C>G)?

AlphaMissense predicts ambiguous (score 0.3466) — an in-silico prediction, not a clinical call.

BMPR2 p.Arg899Gly

c.2695C>G · rs137852741 · VCV2000676

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3466 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
AlphaMissense	0.3466	ambiguous
REVEL	0.476	indeterminate
SaProt	LLR -5.67	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,896 bp · p 0.061 · regional, not allelic
Overall
CADD	22.4	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 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.84e-05% 1/1,461,858 alleles · very rare

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.Arg899Gly
Coding: c.2695C>G
MANE Select: NM_001204
dbSNP: rs137852741
Type: single nucleotide variant
Location: chr2:202556360 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 899: 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); a UniProt-annotated variant site (in pph1; leads to constitutive activation of the mapk14 pathway); the 'disordered' region

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.Arg899Gln Benign ★ same residue
BMPR2 p.Arg899Ter Pathogenic ★★ same residue
BMPR2 p.Arg899Pro Pathogenic ⚠ same residue
BMPR2 c.1128+1G>A Pathogenic ★★ same condition
BMPR2 c.1128+1G>C Pathogenic ★★ same condition
BMPR2 c.621+1G>T Pathogenic/Likely pathogenic ★★ same condition
BMPR2 c.853-2A>G Pathogenic ★★ same condition
BMPR2 p.Arg147Ter 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-arg899gly (accessed [today's date]).

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