Is BMPR2 p.Leu5fs (c.12del) pathogenic?

BMPR2 p.Leu5fs (c.12del) is classified Likely pathogenic in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-15). Absent from gnomAD.

How common is BMPR2 p.Leu5fs (c.12del) in the general population?

BMPR2 p.Leu5fs (c.12del) is absent from gnomAD (gnomAD).

BMPR2 p.Leu5fs

c.12del · rs1690174710 · VCV994099

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 1 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP 1.7, phastCons 0.93

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Leu5fs
Coding: c.12del
MANE Select: NM_001204
dbSNP: rs1690174710
Type: Deletion
Location: chr2:202377486 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB

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

Similar variants

BMPR2 p.Leu5Pro Uncertain significance ★ ⚠ same residue
BMPR2 c.247+1_247+7del Likely pathogenic ★★★ same type
BMPR2 c.247+2del Likely pathogenic ★★★ same type
BMPR2 c.419-38del Benign ★★★ same type
BMPR2 p.Asn861fs Pathogenic ★★ same type
BMPR2 p.Gly390fs Pathogenic/Likely pathogenic ★★ same type
BMPR2 p.Lys230fs Pathogenic ★★ same type
BMPR2 p.Phe773fs 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-leu5fs (accessed [today's date]).

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