Is BMPR1A p.Ile482Val (c.1444A>G) pathogenic?

BMPR1A p.Ile482Val (c.1444A>G) is classified Conflicting classifications of pathogenicity in BMPR1A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.0519); Very rare (popmax 0.00223%, eas); Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Ile482Val (c.1444A>G)?

BMPR1A p.Ile482Val (c.1444A>G) is associated with juvenile polyposis syndrome, polyposis syndrome, hereditary mixed, 2, hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.Ile482Val (c.1444A>G) in the general population?

BMPR1A p.Ile482Val (c.1444A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Juvenile polyposis syndrome inherited?

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

What do computational predictors say about BMPR1A p.Ile482Val (c.1444A>G)?

AlphaMissense predicts likely benign (score 0.0519) — an in-silico prediction, not a clinical call.

BMPR1A p.Ile482Val

c.1444A>G · rs974639091 · VCV460486

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0519 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

juvenile polyposis syndrome

Computational evidence

Protein change
AlphaMissense	0.0519	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -3.5
Regional constraint	o/e 0.51	unconstrained · MANE · 4,412 bp · p 2.1e-15 · regional, not allelic
Overall
CADD	5.107	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,900 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,104 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,900
African / African-American	0.00133%	74,934
European (non-Finnish)	0.000169%	590,023

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.Ile482Val
Coding: c.1444A>G
MANE Select: NM_004329
dbSNP: rs974639091
Type: single nucleotide variant
Location: chr10:86923477 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 482: 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: polyposis syndrome, hereditary mixed, 2 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.Ile482= Benign/Likely benign ★★ same residue
BMPR1A p.Ile482Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
BMPR1A p.Ile482Thr Uncertain significance ★ ⚠ same residue
BMPR1A p.Ile482Leu Likely benign ★ 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-ile482val (accessed [today's date]).

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