Is BMPR2 p.Asn236= (c.708C>T) pathogenic?

BMPR2 p.Asn236= (c.708C>T) is classified Conflicting classifications of pathogenicity in BMPR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-25). Very rare (popmax 0.00102%, nfe); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Asn236= (c.708C>T)?

BMPR2 p.Asn236= (c.708C>T) is associated with Primary pulmonary hypertension, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Asn236= (c.708C>T) in the general population?

BMPR2 p.Asn236= (c.708C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

BMPR2 p.Asn236=

c.708C>T · rs886055470 · VCV333641

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

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 0.36	GERP -1.8, phastCons 0.99
Overall
CADD	6.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,052 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000743% 12/1,614,064 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.Asn236=
Coding: c.708C>T
MANE Select: NM_001204
dbSNP: rs886055470
Type: single nucleotide variant
Location: chr2:202518908 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 236: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); the protein kinase domain; an α-helix

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-asn236 (accessed [today's date]).

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