Is BMPR2 p.Asp323= (c.969T>C) pathogenic?

BMPR2 p.Asp323= (c.969T>C) is classified Likely benign in BMPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-25). Ultra-rare (popmax 0.0178%, eas); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Asp323= (c.969T>C)?

BMPR2 p.Asp323= (c.969T>C) is associated with Primary pulmonary hypertension (ClinVar).

How common is BMPR2 p.Asp323= (c.969T>C) in the general population?

BMPR2 p.Asp323= (c.969T>C) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

BMPR2 p.Asp323=

c.969T>C · rs780884801 · VCV2723560

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

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 3.5	GERP 0.27, phastCons 1
Overall
CADD	14.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,850 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000497% 8/1,609,526 alleles · ultra-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.Asp323=
Coding: c.969T>C
MANE Select: NM_001204
dbSNP: rs780884801
Type: single nucleotide variant
Location: chr2:202530795 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 323: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); the protein kinase domain; a UniProt-annotated variant site (in pph1; loss of localization to the plasma membrane; localized to the cytoplasm); 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

Similar variants

BMPR2 c.1128+1G>A Pathogenic ★★ same condition
BMPR2 c.1128+1G>C Pathogenic ★★ same condition
BMPR2 c.621+1G>T Pathogenic/Likely pathogenic ★★ same condition
BMPR2 c.853-2A>G Pathogenic ★★ same condition
BMPR2 p.Arg147Ter Pathogenic ★★ same condition
BMPR2 p.Arg213Ter Pathogenic ★★ same condition
BMPR2 p.Arg491Trp Pathogenic ★★ same condition
BMPR2 p.Arg873Ter Pathogenic/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-asp323 (accessed [today's date]).

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