Is BMPR2 p.Glu243Lys (c.727G>A) pathogenic?

BMPR2 p.Glu243Lys (c.727G>A) is classified Uncertain significance in BMPR2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-24). AlphaMissense: likely pathogenic (0.9967); Absent from gnomAD v4.1; Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Glu243Lys (c.727G>A)?

BMPR2 p.Glu243Lys (c.727G>A) is associated with Primary pulmonary hypertension, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Glu243Lys (c.727G>A) in the general population?

BMPR2 p.Glu243Lys (c.727G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMPR2 p.Glu243Lys (c.727G>A)?

AlphaMissense predicts likely pathogenic (score 0.9967) — an in-silico prediction, not a clinical call.

BMPR2 p.Glu243Lys

c.727G>A · rs1085307254 · VCV425817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9967 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,190)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
AlphaMissense	0.9967	likely pathogenic · top 4% in BMPR2
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -16.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,190). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BMPR2
Protein: p.Glu243Lys
Coding: c.727G>A
MANE Select: NM_001204
dbSNP: rs1085307254
Type: single nucleotide variant
Location: chr2:202518927 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 243: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); the protein kinase domain; 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

Also linked: pulmonary hypertension, primary, 1

Similar variants

BMPR2 p.Glu243Gln Pathogenic same residue
BMPR2 p.Glu243Ter Pathogenic same residue
BMPR2 p.Glu243= Likely benign ★ 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

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-glu243lys (accessed [today's date]).

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