Is BMPR1A p.Pro201= (c.603A>G) pathogenic?

BMPR1A p.Pro201= (c.603A>G) is classified Conflicting classifications of pathogenicity in BMPR1A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-08-01). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BMPR1A p.Pro201= (c.603A>G)?

BMPR1A p.Pro201= (c.603A>G) is associated with hereditary neoplastic syndrome, juvenile polyposis syndrome (ClinVar).

How common is BMPR1A p.Pro201= (c.603A>G) in the general population?

BMPR1A p.Pro201= (c.603A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

BMPR1A p.Pro201=

c.603A>G · rs2133545231 · VCV1330036

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.52	GERP -5.7
Overall
CADD	7.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,836 alleles

Overall 0.000124% 2/1,614,020 alleles · very rare exomes 2/1,461,714 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,836
African / African-American	0.00133%	75,038

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.Pro201=
Coding: c.603A>G
MANE Select: NM_004329
dbSNP: rs2133545231
Type: single nucleotide variant
Location: chr10:86912312 (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

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

Also linked: juvenile polyposis syndrome

Similar variants

BMPR1A p.Pro201Leu Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro201Ala Uncertain significance ★ ⚠ same residue
BMPR1A p.Pro201Thr 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-pro201 (accessed [today's date]).

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