Is BMPR1A p.Phe433= (c.1299C>T) pathogenic?

BMPR1A p.Phe433= (c.1299C>T) is classified Benign/Likely benign in BMPR1A (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-05-01). Rare (popmax 0.525%, afr); Associated with polyposis syndrome, hereditary mixed, 2.

What condition is associated with BMPR1A p.Phe433= (c.1299C>T)?

BMPR1A p.Phe433= (c.1299C>T) is associated with polyposis syndrome, hereditary mixed, 2, hereditary neoplastic syndrome, juvenile polyposis syndrome (ClinVar).

How common is BMPR1A p.Phe433= (c.1299C>T) in the general population?

BMPR1A p.Phe433= (c.1299C>T) is rare (popmax 0.525%, afr) (gnomAD).

How is Hereditary mixed polyposis syndrome inherited?

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

BMPR1A p.Phe433=

c.1299C>T · rs150946485 · VCV136525

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

rare (popmax 0.525%, afr)

Conditions

polyposis syndrome, hereditary mixed, 2

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 -0.18	GERP -3.8, phastCons 0.66
Overall
CADD	10.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.525% African / African-American · 394/75,032 alleles

Filtering AF 0.482% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.466%

Overall 0.0338% 545/1,614,170 alleles · rare exomes 327/1,461,876 · genomes 218/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.525%	190
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Admixed American	0.0766%	1,305
Middle Eastern	0.0495%	2,021
East Asian	0.00668%	14,962
South Asian	0.00439%	22,770
European (non-Finnish)	0.00347%	28,781

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.Phe433=
Coding: c.1299C>T
MANE Select: NM_004329
dbSNP: rs150946485
Type: single nucleotide variant
Location: chr10:86921652 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 433: the protein kinase domain

Full BMPR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polyposis syndrome, hereditary mixed, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome juvenile polyposis syndrome

For Hereditary mixed polyposis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

BMPR1A p.Phe433Leu Uncertain significance ★★ ⚠ same residue
BMPR1A p.Phe433Cys 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
BMPR1A c.333+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-phe433 (accessed [today's date]).

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