Is BMPR2 p.Ser27= (c.81G>A) pathogenic?

BMPR2 p.Ser27= (c.81G>A) is classified Benign/Likely benign in BMPR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-02). Very rare (popmax 0.00802%, afr); Associated with pulmonary hypertension, primary, 1.

What condition is associated with BMPR2 p.Ser27= (c.81G>A)?

BMPR2 p.Ser27= (c.81G>A) is associated with pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Ser27= (c.81G>A) in the general population?

BMPR2 p.Ser27= (c.81G>A) is very rare (popmax 0.00802%, afr) (gnomAD).

BMPR2 p.Ser27=

c.81G>A · rs147207234 · VCV895426

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00802%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -3.4, phastCons 0.26
Overall
CADD	8.273	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00802% African / African-American · 6/74,780 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.0018% 29/1,608,782 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00802%	12,463
East Asian	0.00447%	22,381
Remaining individualsnot grpmax-eligible	0.00321%	31,146
South Asian	0.00224%	44,742
European (non-Finnish)	0.00144%	69,277

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.Ser27=
Coding: c.81G>A
MANE Select: NM_001204
dbSNP: rs147207234
Type: single nucleotide variant
Location: chr2:202464813 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 27: a turn

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

Similar variants

BMPR2 p.Ser27Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ser27 (accessed [today's date]).

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