Is BMPR2 p.Val217fs (c.648_658delinsGATATGGAC) pathogenic?

BMPR2 p.Val217fs (c.648658delinsGATATGGAC) is classified Pathogenic in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01).

BMPR2 p.Val217fs

c.648_658delinsGATATGGAC · VCV3390288

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 6 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP -0.86, phastCons 1

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

Variant & gene context

Gene: BMPR2
Protein: p.Val217fs
Coding: c.648_658delinsGATATGGAC
MANE Select: NM_001204
Type: Indel
Location: chr2:202518848 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 217: a binding site; the protein kinase domain; a β-strand

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

Similar variants

BMPR2 c.77-1_77delinsAA Likely pathogenic ★ same type
BMPR2 p.Phe424_Gly426delinsTer Likely pathogenic ★ same type
BMPR2 p.Tyr282fs Pathogenic ★ same type
BMPR2 p.Asn1036fs Uncertain significance ★ same type
BMPR2 c.248-5_248delinsAC Pathogenic same type
BMPR2 c.248-592_413delinsGTAAAGTA Pathogenic same type
BMPR2 c.418+2_418+4delinsGAG Pathogenic same type
BMPR2 c.-947_-946delinsAT Pathogenic same type

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-val217fs (accessed [today's date]).

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