Is BMPR1A p.Pro465fs (c.1394del) pathogenic?

BMPR1A p.Pro465fs (c.1394del) is classified Pathogenic/Likely pathogenic in BMPR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-06). Absent from gnomAD; Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Pro465fs (c.1394del)?

BMPR1A p.Pro465fs (c.1394del) is associated with juvenile polyposis syndrome (ClinVar).

How common is BMPR1A p.Pro465fs (c.1394del) in the general population?

BMPR1A p.Pro465fs (c.1394del) is absent from gnomAD (gnomAD).

How is Juvenile polyposis syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

BMPR1A p.Pro465fs

c.1394del · rs2539648615 · VCV2673911

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

juvenile polyposis syndrome

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 12 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.46	GERP -2.6, phastCons 0.079
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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: BMPR1A
Protein: p.Pro465fs
Coding: c.1394del
MANE Select: NM_004329
dbSNP: rs2539648615
Type: Deletion
Location: chr10:86923426 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 465: the protein kinase domain

Full BMPR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

juvenile polyposis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Juvenile polyposis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

BMPR1A p.Pro465Leu Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro465= Benign/Likely benign ★★ same residue
BMPR1A c.676delG Pathogenic/Likely pathogenic ★★ same condition
BMPR1A p.Arg152fs Pathogenic ★★ same condition
BMPR1A p.Glu256fs Pathogenic ★★ same condition
BMPR1A p.Glu276fs Pathogenic ★★ same condition
BMPR1A p.Glu45fs Pathogenic ★★ same condition
BMPR1A p.Gly92fs 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/bmpr1a-p-pro465fs (accessed [today's date]).

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