Is BMPR2 p.Asn29Ser (c.86A>G) pathogenic?

BMPR2 p.Asn29Ser (c.86A>G) is classified Likely benign in BMPR2 (ClinVar, Expert panel, 7 submitters; last evaluated 2024-09-10). AlphaMissense: likely benign (0.0739); Rare (popmax 0.767%, afr); Associated with pulmonary arterial hypertension.

What condition is associated with BMPR2 p.Asn29Ser (c.86A>G)?

BMPR2 p.Asn29Ser (c.86A>G) is associated with pulmonary arterial hypertension, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Asn29Ser (c.86A>G) in the general population?

BMPR2 p.Asn29Ser (c.86A>G) is rare (popmax 0.767%, afr) (gnomAD).

What do computational predictors say about BMPR2 p.Asn29Ser (c.86A>G)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

BMPR2 p.Asn29Ser

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.86A>G · rs112862820 · VCV333638

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.767%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pulmonary arterial hypertension

ClinGen expert panel — Pulmonary Hypertension VCEP

Likely Benign for pulmonary arterial hypertension. Applied ACMG criteria (verbatim):

BS1

Curation rationale (ClinGen, verbatim)

The BMPR2 c.86A>G missense variant is predicted to cause a substitution of asparagine to serine at amino acid position 29 (p.Asn29Ser) in exon 2 within the signal peptide domain. The highest population minor allele frequency in gnomAD v2.1.1 controls is 0.006265 (v4.1.0 is 0.007668) in African/African American population, which is higher than the ClinGen Pulmonary Hypertension VECP threshold ≥0.1% for BS1, and therefore meets this criterion. The computational predictor REVEL gives a score of 0.497 indicating neither PP3 (≥0.75) nor BP4 (≤0.25) met. SpliceAI algorithm predicts no deleterious effect on acceptor or donor splice site. In summary, the variant meets the criteria to be classified as variant of likely benign for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BS1 (VCEP specification version 1.1, 1/18/2024).

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

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -5.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 153 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	15.6	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 0.767% African / African-American · 575/74,988 alleles

Filtering AF 0.715% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.694%

Overall 0.0414% 668/1,612,138 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.767%	130
Middle Eastern	0.0826%	1,211
Remaining individualsnot grpmax-eligible	0.0817%	1,224
Admixed American	0.0435%	2,299
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,556
European (non-Finnish)	0.000848%	117,931

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.Asn29Ser
Coding: c.86A>G
MANE Select: NM_001204
dbSNP: rs112862820
Type: single nucleotide variant
Location: chr2:202464818 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 29: a turn

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)

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+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-asn29ser (accessed [today's date]).

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