Is BMPR2 p.Arg886His (c.2657G>A) pathogenic?

BMPR2 p.Arg886His (c.2657G>A) is classified Benign in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-31). AlphaMissense: likely benign (0.106); Very rare (popmax 0.00602%, nfe); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Arg886His (c.2657G>A)?

BMPR2 p.Arg886His (c.2657G>A) is associated with Primary pulmonary hypertension (ClinVar).

How common is BMPR2 p.Arg886His (c.2657G>A) in the general population?

BMPR2 p.Arg886His (c.2657G>A) is very rare (popmax 0.00602%, nfe) (gnomAD).

What do computational predictors say about BMPR2 p.Arg886His (c.2657G>A)?

AlphaMissense predicts likely benign (score 0.106) — an in-silico prediction, not a clinical call.

BMPR2 p.Arg886His

c.2657G>A · VCV3630562

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.106 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
AlphaMissense	0.106	likely benign
REVEL	0.408	indeterminate
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL 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 0.92	unconstrained · MANE · 6,896 bp · p 0.061 · regional, not allelic
Overall
CADD	25.3	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 0.00602% European (non-Finnish) · 71/1,180,050 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00477% 77/1,614,104 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,620
Remaining individualsnot grpmax-eligible	0.0032%	31,244
Finnishnot grpmax-eligible	0.00312%	32,020
Admixed American	0.00167%	60,004
South Asian	0.0011%	91,078

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.Arg886His
Coding: c.2657G>A
MANE Select: NM_001204
Type: single nucleotide variant
Location: chr2:202556322 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 886: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); a UniProt-annotated variant site (in pph1; loss of localization to the plasma membrane; localized to the cytoplasm); the 'disordered' region

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 p.Arg886Cys Likely benign ★★★ same residue
BMPR2 p.Arg886Ser Uncertain significance ★ same residue
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

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-arg886his (accessed [today's date]).

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