Is BMPR2 p.Gly182Asp (c.545G>A) pathogenic?

BMPR2 p.Gly182Asp (c.545G>A) is classified Uncertain significance in BMPR2 (ClinVar, Expert panel, 8 submitters; last evaluated 2026-01-30). AlphaMissense: ambiguous (0.4252); Ultra-rare (popmax 0.0329%, nfe); Associated with pulmonary arterial hypertension.

What condition is associated with BMPR2 p.Gly182Asp (c.545G>A)?

BMPR2 p.Gly182Asp (c.545G>A) is associated with pulmonary arterial hypertension, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Gly182Asp (c.545G>A) in the general population?

BMPR2 p.Gly182Asp (c.545G>A) is ultra-rare (popmax 0.0329%, nfe) (gnomAD).

What do computational predictors say about BMPR2 p.Gly182Asp (c.545G>A)?

AlphaMissense predicts ambiguous (score 0.4252) — an in-silico prediction, not a clinical call.

BMPR2 p.Gly182Asp

Q: How is Idiopathic/heritable pulmonary arterial hypertension inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.545G>A · rs137852754 · VCV8813

Uncertain significance Expert panel

Classification

Uncertain significance

ClinVar

Review

Expert panel ★★★☆

ClinVar · 8 submitters

AlphaMissense

ambiguous

0.4252 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

pulmonary arterial hypertension

ClinGen expert panel — Pulmonary Hypertension VCEP

Uncertain Significance for pulmonary arterial hypertension. Applied ACMG criteria (verbatim):

BS3

Curation rationale (ClinGen, verbatim)

The NM_0001204.7(BMPR2) c.545G>A variant is a missense variant predicted to cause substitution of glycine by aspartic acid at amino acid 182 (p.Gly182Asp). The highest subpopulation minor allele frequency in gnomAD v2.1.1 (controls) is 0.0003507 in the European (non-Finnish) population, which is higher than the ClinGen PH VCEP threshold (<0.01%) for PM2 but lower than the threshold (>0.1%) for BS1. A similar AF in gnomAD v4.1 (non-Finnish Europeans, 388/1179912) confirms the non-application of PM2 (PM2 not met). Computational prediction tool scores (REVEL 0.8069, AlphaMissense 0.4252, CADD 16.92) did not yield two out of three of these above the PH VCEP thresholds (PP3 not met). Luciferase assay data indicated that variant transcriptional activity was comparable to wild-type, indicating no deleterious effect (BS3; PMID: 18321866). In summary, this variant meets the criteria to be classified as likely benign for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: no criteria scored. (VCEP specifications version 2.0, 1/30/2026)

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
AlphaMissense	0.4252	ambiguous
REVEL	0.807	moderately pathogenic-leaning
SaProt	LLR -5.83	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 153 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	28.0	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 0.0329% European (non-Finnish) · 388/1,179,912 alleles

Filtering AF 0.0302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0291%

Overall 0.0253% 408/1,613,798 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.0256%	3,905
African / African-American	0.00534%	18,721

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.Gly182Asp
Coding: c.545G>A
MANE Select: NM_001204
dbSNP: rs137852754
Type: single nucleotide variant
Location: chr2:202514903 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 182: a UniProt-annotated variant site (in pph1; likely benign)

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

Disease context

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

Also linked: pulmonary hypertension, primary, 1

For Idiopathic/heritable pulmonary arterial hypertension (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

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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+5G>A 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-gly182asp (accessed [today's date]).

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