Is BMPR1A p.Pro145= (c.435G>A) pathogenic?

BMPR1A p.Pro145= (c.435G>A) is classified Benign in BMPR1A (ClinVar, Multiple submitters, 22 submitters; last evaluated 2026-02-04). Common (popmax 14%, afr) — too common for a highly-penetrant pathogenic allele; Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Pro145= (c.435G>A)?

BMPR1A p.Pro145= (c.435G>A) is associated with juvenile polyposis syndrome, generalized juvenile polyposis/juvenile polyposis coli, polyposis syndrome, hereditary mixed, 2 (ClinVar).

How is Juvenile polyposis syndrome inherited?

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

BMPR1A p.Pro145=

Q: How common is BMPR1A p.Pro145= (c.435G>A) in the general population?

BMPR1A p.Pro145= (c.435G>A) is common (popmax 14%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.435G>A · rs11818239 · VCV183708

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 22 submitters

gnomAD v4.1

Common

common (popmax 14%, afr) — too common for a highly-penetrant pathogenic allele

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 -2.5	GERP -5.1
Overall
CADD	1.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14% African / African-American · 10,526/74,992 alleles

Filtering AF 13.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.7%

Overall 0.762% 12,291/1,614,050 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14%	7
Remaining individualsnot grpmax-eligible	1.09%	91
Admixed American	1.08%	92
Middle Eastern	0.99%	101
South Asian	0.0351%	2,846
European (non-Finnish)	0.0283%	3,533
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801
Finnishnot grpmax-eligible	0.00313%	31,993
East Asian	0.00223%	44,882

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.Pro145=
Coding: c.435G>A
MANE Select: NM_004329
dbSNP: rs11818239
Type: single nucleotide variant
Location: chr10:86900031 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB

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 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.Pro145Leu Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro145Ser Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro145Gln Uncertain significance ★ ⚠ same residue
BMPR1A p.Pro145Thr 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

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-pro145 (accessed [today's date]).

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