Is BMPR1A p.Ser39fs (c.115_116insA) pathogenic?

BMPR1A p.Ser39fs (c.115116insA) is classified Likely pathogenic in BMPR1A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-07-24). Absent from gnomAD; Associated with generalized juvenile polyposis/juvenile polyposis coli.

What condition is associated with BMPR1A p.Ser39fs (c.115_116insA)?

BMPR1A p.Ser39fs (c.115_116insA) is associated with generalized juvenile polyposis/juvenile polyposis coli (ClinVar).

How common is BMPR1A p.Ser39fs (c.115_116insA) in the general population?

BMPR1A p.Ser39fs (c.115_116insA) 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.Ser39fs

c.115_116insA · rs587783038 · VCV156485

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

generalized juvenile polyposis/juvenile polyposis coli

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 4 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP 0.15, phastCons 1

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.Ser39fs
Coding: c.115_116insA
MANE Select: NM_004329
dbSNP: rs587783038
Type: Insertion
Location: chr10:86890109 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB

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

Disease context

generalized juvenile polyposis/juvenile polyposis coli — 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.Ser39Cys Uncertain significance ★★ ⚠ same residue
BMPR1A p.Ser39Phe Uncertain significance ★★ ⚠ same residue
BMPR1A p.Ser39= Benign/Likely benign ★★ same residue
BMPR1A p.Ser37_Asp38insHisGlyThrGlyIle Pathogenic ★ same condition
BMPR1A p.Ser39Tyr Uncertain significance ★ ⚠ same residue
BMPR1A p.Arg119Cys Pathogenic/Likely pathogenic ★★ same condition
BMPR1A p.Arg228Ter Pathogenic ★★ same condition
BMPR1A p.Arg361Ter 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-ser39fs (accessed [today's date]).

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