Is BMPR1A p.Arg478= (c.1434T>A) pathogenic?

BMPR1A p.Arg478= (c.1434T>A) is classified Benign/Likely benign in BMPR1A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-27). Absent from gnomAD v4.1; Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Arg478= (c.1434T>A)?

BMPR1A p.Arg478= (c.1434T>A) is associated with juvenile polyposis syndrome (ClinVar).

How common is BMPR1A p.Arg478= (c.1434T>A) in the general population?

BMPR1A p.Arg478= (c.1434T>A) is absent from gnomAD v4.1 (gnomAD).

How is Juvenile polyposis syndrome inherited?

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

BMPR1A p.Arg478=

c.1434T>A · rs1057521680 · VCV383573

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -2.7	GERP -3.8
Overall
CADD	3.868	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMPR1A
Protein: p.Arg478=
Coding: c.1434T>A
MANE Select: NM_004329
dbSNP: rs1057521680
Type: single nucleotide variant
Location: chr10:86923467 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 478: 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.Arg478Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BMPR1A p.Arg478His Conflicting classifications of pathogenicity ★ ⚠ same residue
BMPR1A p.Arg478Leu 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-arg478 (accessed [today's date]).

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