Is BMPR2 p.Arg934Thr (c.2801G>C) pathogenic?

BMPR2 p.Arg934Thr (c.2801G>C) is classified Likely benign in BMPR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-02). AlphaMissense: likely pathogenic (0.6089); Very rare (popmax 0.0022%, sas); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Arg934Thr (c.2801G>C)?

BMPR2 p.Arg934Thr (c.2801G>C) is associated with Primary pulmonary hypertension, pulmonary venoocclusive disease 1, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Arg934Thr (c.2801G>C) in the general population?

BMPR2 p.Arg934Thr (c.2801G>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BMPR2 p.Arg934Thr (c.2801G>C)?

AlphaMissense predicts likely pathogenic (score 0.6089) — an in-silico prediction, not a clinical call.

BMPR2 p.Arg934Thr

c.2801G>C · rs575479720 · VCV333650

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6089 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
AlphaMissense	0.6089	likely pathogenic
REVEL	0.469	indeterminate
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,896 bp · p 0.061 · regional, not allelic
Overall
CADD	25.0	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 · 2/91,078 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00248% 40/1,614,212 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,741
Remaining individualsnot grpmax-eligible	0.0032%	31,255
South Asiangrpmax	0.0022%	45,539
European (non-Finnish)	0.00161%	62,108

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg934Thr
Coding: c.2801G>C
MANE Select: NM_001204
dbSNP: rs575479720
Type: single nucleotide variant
Location: chr2:202556466 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 934: 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); 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

Also linked: pulmonary venoocclusive disease 1 pulmonary hypertension, primary, 1

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+6T>G 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-arg934thr (accessed [today's date]).

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