Is BMPR1A p.Pro356= (c.1068C>T) pathogenic?

BMPR1A p.Pro356= (c.1068C>T) is classified Conflicting classifications of pathogenicity in BMPR1A (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-04-01). Very rare (popmax 0.00483%, nfe); Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Pro356= (c.1068C>T)?

BMPR1A p.Pro356= (c.1068C>T) is associated with juvenile polyposis syndrome, generalized juvenile polyposis/juvenile polyposis coli, hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.Pro356= (c.1068C>T) in the general population?

BMPR1A p.Pro356= (c.1068C>T) is very rare (popmax 0.00483%, nfe) (gnomAD).

How is Juvenile polyposis syndrome inherited?

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

BMPR1A p.Pro356=

c.1068C>T · rs759520915 · VCV230618

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

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 -0.47	GERP -3.8, phastCons 0.15
Overall
CADD	12.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00483% European (non-Finnish) · 57/1,179,830 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00391% 63/1,612,960 alleles · very rare exomes 60/1,460,794 · genomes 3/152,166 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,699
Remaining individualsnot grpmax-eligible	0.00321%	31,198
East Asian	0.00223%	44,902
Admixed American	0.00167%	59,988
African / African-American	0.00134%	74,864
South Asian	0.0011%	91,032

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.Pro356=
Coding: c.1068C>T
MANE Select: NM_004329
dbSNP: rs759520915
Type: single nucleotide variant
Location: chr10:86919371 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 356: 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: generalized juvenile polyposis/juvenile polyposis coli 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.Pro356Arg Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro356Ser Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro356Thr 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-pro356 (accessed [today's date]).

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