Is BMPR2 p.Leu916= (c.2748T>C) pathogenic?

BMPR2 p.Leu916= (c.2748T>C) is classified Benign/Likely benign in BMPR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1.34%, afr); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Leu916= (c.2748T>C)?

BMPR2 p.Leu916= (c.2748T>C) is associated with Primary pulmonary hypertension, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Leu916= (c.2748T>C) in the general population?

BMPR2 p.Leu916= (c.2748T>C) is low-frequency (popmax 1.34%, afr) (gnomAD).

BMPR2 p.Leu916=

c.2748T>C · rs16839188 · VCV333649

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.34%, afr)

Conditions

Primary pulmonary hypertension

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 0.15	GERP -2.7
Overall
CADD	4.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.34% African / African-American · 1,002/75,002 alleles

Filtering AF 1.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.24%

Overall 0.0661% 1,067/1,614,132 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.34%	75
Remaining individualsnot grpmax-eligible	0.0448%	2,232
Admixed American	0.0367%	2,728
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.0011%	90,771
South Asian	0.0011%	91,086

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.Leu916=
Coding: c.2748T>C
MANE Select: NM_001204
dbSNP: rs16839188
Type: single nucleotide variant
Location: chr2:202556413 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 916: 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 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-leu916 (accessed [today's date]).

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