Is BMPR1A p.Arg486Trp (c.1456C>T) pathogenic?

BMPR1A p.Arg486Trp (c.1456C>T) is classified Conflicting classifications of pathogenicity in BMPR1A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-12-10). AlphaMissense: likely pathogenic (0.7023); Ultra-rare (popmax 0.0329%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with BMPR1A p.Arg486Trp (c.1456C>T)?

BMPR1A p.Arg486Trp (c.1456C>T) is associated with hereditary neoplastic syndrome, polyposis syndrome, hereditary mixed, 2, juvenile polyposis syndrome (ClinVar).

How common is BMPR1A p.Arg486Trp (c.1456C>T) in the general population?

BMPR1A p.Arg486Trp (c.1456C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about BMPR1A p.Arg486Trp (c.1456C>T)?

AlphaMissense predicts likely pathogenic (score 0.7023) — an in-silico prediction, not a clinical call.

BMPR1A p.Arg486Trp

c.1456C>T · rs767763451 · VCV460487

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.7023 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7023	likely pathogenic
REVEL	0.414	indeterminate
SaProt	LLR -13.25	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1.4, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 4,412 bp · p 2.1e-15 · regional, not allelic
Overall
CADD	25.9	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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00105% 17/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
African / African-American	0.00267%	37,460
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,078
European (non-Finnish)	0.000932%	107,276

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.Arg486Trp
Coding: c.1456C>T
MANE Select: NM_004329
dbSNP: rs767763451
Type: single nucleotide variant
Location: chr10:86923489 (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

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

Also linked: polyposis syndrome, hereditary mixed, 2 juvenile polyposis syndrome

Similar variants

BMPR1A p.Arg486Gln Uncertain significance ★★ same residue
BMPR1A p.Arg486= Likely benign ★★ same residue
BMPR1A p.Arg486Leu Uncertain significance ★ ⚠ 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-arg486trp (accessed [today's date]).

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