Is BMPR2 p.Leu183= (c.549T>C) pathogenic?

BMPR2 p.Leu183= (c.549T>C) is classified Benign/Likely benign in BMPR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.0974%, afr); Associated with pulmonary hypertension, primary, 1.

What condition is associated with BMPR2 p.Leu183= (c.549T>C)?

BMPR2 p.Leu183= (c.549T>C) is associated with pulmonary hypertension, primary, 1, pulmonary venoocclusive disease 1 (ClinVar).

How common is BMPR2 p.Leu183= (c.549T>C) in the general population?

BMPR2 p.Leu183= (c.549T>C) is ultra-rare (popmax 0.0974%, afr) (gnomAD).

BMPR2 p.Leu183=

c.549T>C · rs142769493 · VCV896823

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0974%, afr)

Conditions

pulmonary hypertension, primary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.79	GERP -4.3, phastCons 1
Overall
CADD	6.913	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0974% African / African-American · 73/74,926 alleles

Filtering AF 0.0794% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0728%

Overall 0.00477% 77/1,613,966 alleles · ultra-rare exomes 42/1,461,784 · genomes 35/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0974%	1,026
Remaining individualsnot grpmax-eligible	0.0032%	31,243
South Asian	0.0022%	45,541

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.Leu183=
Coding: c.549T>C
MANE Select: NM_001204
dbSNP: rs142769493
Type: single nucleotide variant
Location: chr2:202514907 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB

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 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-leu183 (accessed [today's date]).

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