Is BMPR1A p.Arg486= (c.1458G>A) pathogenic?

BMPR1A p.Arg486= (c.1458G>A) is classified Likely benign in BMPR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-01). Very rare (popmax 8.47e-05%, nfe); Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Arg486= (c.1458G>A)?

BMPR1A p.Arg486= (c.1458G>A) is associated with juvenile polyposis syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.Arg486= (c.1458G>A) in the general population?

BMPR1A p.Arg486= (c.1458G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Juvenile polyposis syndrome inherited?

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

BMPR1A p.Arg486=

c.1458G>A · rs1355650385 · VCV1148264

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

juvenile polyposis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.71	GERP -3.8
Overall
CADD	3.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,036 alleles

Overall 0.000124% 2/1,614,216 alleles · very rare exomes 2/1,461,892 · genomes 0/152,324 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)grpmax	8.47e-05%	1,180,036

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg486=
Coding: c.1458G>A
MANE Select: NM_004329
dbSNP: rs1355650385
Type: single nucleotide variant
Location: chr10:86923491 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 486: a UniProt-annotated variant site (in a gastric adenocarcinoma sample; somatic mutation); 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

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.Arg486Gln Uncertain significance ★★ same residue
BMPR1A p.Arg486Leu Uncertain significance ★ ⚠ same residue
BMPR1A p.Arg486Trp Conflicting classifications of pathogenicity ★ ⚠ 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
BMPR1A c.230+1G>A 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-arg486 (accessed [today's date]).

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