Is BMPR1A p.Ile482Phe (c.1444A>T) pathogenic?

BMPR1A p.Ile482Phe (c.1444A>T) is classified Conflicting classifications of pathogenicity in BMPR1A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-03-24). AlphaMissense: likely benign (0.1296); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BMPR1A p.Ile482Phe (c.1444A>T)?

BMPR1A p.Ile482Phe (c.1444A>T) is associated with hereditary neoplastic syndrome, polyposis syndrome, hereditary mixed, 2 (ClinVar).

How common is BMPR1A p.Ile482Phe (c.1444A>T) in the general population?

BMPR1A p.Ile482Phe (c.1444A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMPR1A p.Ile482Phe (c.1444A>T)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

BMPR1A p.Ile482Phe

c.1444A>T · rs974639091 · VCV2680197

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -7.10	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	14.1	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

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.Ile482Phe
Coding: c.1444A>T
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

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

Also linked: polyposis syndrome, hereditary mixed, 2

Similar variants

BMPR1A p.Ile482= Benign/Likely benign ★★ same residue
BMPR1A p.Ile482Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BMPR1A p.Ile482Leu Likely benign ★ same residue
BMPR1A p.Ile482Thr Uncertain significance ★ ⚠ same residue
BMPR1A c.1166+1G>A 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-ile482phe (accessed [today's date]).

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