Is BMPR1A p.Arg9= (c.27A>G) pathogenic?

BMPR1A p.Arg9= (c.27A>G) is classified Conflicting classifications of pathogenicity in BMPR1A (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-08-28). Ultra-rare (popmax 0.0112%, eas); Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Arg9= (c.27A>G)?

BMPR1A p.Arg9= (c.27A>G) is associated with juvenile polyposis syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.Arg9= (c.27A>G) in the general population?

BMPR1A p.Arg9= (c.27A>G) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

How is Juvenile polyposis syndrome inherited?

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

BMPR1A p.Arg9=

c.27A>G · rs751420248 · VCV383960

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Conditions

juvenile polyposis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP 0.13, phastCons 0.46
Overall
CADD	5.556	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,826 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000372% 6/1,611,852 alleles · ultra-rare exomes 6/1,459,518 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,965
Admixed American	0.00167%	60,018

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BMPR1A
Protein: p.Arg9=
Coding: c.27A>G
MANE Select: NM_004329
dbSNP: rs751420248
Type: single nucleotide variant
Location: chr10:86876045 (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

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

Also linked: hereditary neoplastic syndrome

For Juvenile polyposis syndrome (Orphanet):

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

Similar variants

BMPR1A p.Arg9Ter Pathogenic/Likely pathogenic ★★ same residue
BMPR1A p.Arg9Lys Uncertain significance ★★ ⚠ same residue
BMPR1A p.Arg9Thr Uncertain significance ★★ ⚠ same residue
BMPR1A p.Arg9fs Likely pathogenic ★ same residue
BMPR1A c.1166+1G>A Likely pathogenic ★★ same condition
BMPR1A c.1343-2A>G Likely pathogenic ★★ same condition
BMPR1A c.1473+1G>A Pathogenic/Likely pathogenic ★★ same condition
BMPR1A c.1473+1G>C Pathogenic/Likely 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-arg9 (accessed [today's date]).

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