Is BMPR1A p.Cys61= (c.183C>T) pathogenic?

BMPR1A p.Cys61= (c.183C>T) is classified Conflicting classifications of pathogenicity in BMPR1A (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-10-27). Ultra-rare (popmax 0.0164%, mid); Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Cys61= (c.183C>T)?

BMPR1A p.Cys61= (c.183C>T) is associated with juvenile polyposis syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.Cys61= (c.183C>T) in the general population?

BMPR1A p.Cys61= (c.183C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Juvenile polyposis syndrome inherited?

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

BMPR1A p.Cys61=

c.183C>T · rs140610221 · VCV482845

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 1.8	GERP 0.17, phastCons 1
Overall
CADD	11.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.0018% 29/1,613,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.004%	24,972
European (non-Finnish)	0.00203%	49,168
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Cys61=
Coding: c.183C>T
MANE Select: NM_004329
dbSNP: rs140610221
Type: single nucleotide variant
Location: chr10:86890177 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 61: a disulfide bond; a β-strand

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: 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.Cys61Tyr 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
BMPR1A c.430+1G>A 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-cys61 (accessed [today's date]).

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