Is BMPR2 p.Met505fs (c.1513_1514insAA) pathogenic?

BMPR2 p.Met505fs (c.15131514insAA) is classified Pathogenic in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-16). Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Met505fs (c.1513_1514insAA)?

BMPR2 p.Met505fs (c.1513_1514insAA) is associated with Primary pulmonary hypertension (ClinVar).

BMPR2 p.Met505fs

c.1513_1514insAA · VCV3717470

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -5.4, phastCons 0.003

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BMPR2
Protein: p.Met505fs
Coding: c.1513_1514insAA
MANE Select: NM_001204
Type: Insertion
Location: chr2:202552814 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 505: an α-helix; 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)

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.Met505Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BMPR2 p.Met505Arg Uncertain significance ★ same residue
BMPR2 p.Met505Ile Uncertain significance ★ ⚠ same residue
BMPR2 p.Met505Val 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

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-met505fs (accessed [today's date]).

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