Is BMPR2 p.Arg272His (c.815G>A) pathogenic?

BMPR2 p.Arg272His (c.815G>A) is classified Conflicting classifications of pathogenicity in BMPR2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-06-08). AlphaMissense: likely benign (0.1249); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with BMPR2 p.Arg272His (c.815G>A)?

BMPR2 p.Arg272His (c.815G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BMPR2 p.Arg272His (c.815G>A) in the general population?

BMPR2 p.Arg272His (c.815G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BMPR2 p.Arg272His (c.815G>A)?

AlphaMissense predicts likely benign (score 0.1249) — an in-silico prediction, not a clinical call.

BMPR2 p.Arg272His

c.815G>A · rs748889215 · VCV2737723

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1249 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1249	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -6.74	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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 153 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	25.6	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 0.0022% South Asian · 2/91,090 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000372% 6/1,613,954 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,545
Finnishnot grpmax-eligible	0.00156%	63,978
European (non-Finnish)	0.000254%	393,331

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.Arg272His
Coding: c.815G>A
MANE Select: NM_001204
dbSNP: rs748889215
Type: single nucleotide variant
Location: chr2:202519015 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 272: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); the protein kinase domain

Full BMPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMPR2 p.Arg272= Likely benign ★ same residue
BMPR2 p.Ala35Val Uncertain significance ★★ ⚠ same condition
BMPR2 p.Arg114His Uncertain significance ★★ ⚠ same condition
BMPR2 p.Arg357Lys Uncertain significance ★★ ⚠ same condition
BMPR2 p.Arg857Trp Uncertain significance ★★ ⚠ same condition
BMPR2 p.Asn588Ser Uncertain significance ★★ ⚠ same condition
BMPR2 p.Asp682Glu Uncertain significance ★★ ⚠ same condition
BMPR2 p.Gln834Arg Uncertain significance ★★ ⚠ 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-arg272his (accessed [today's date]).

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