Is BMPR1A p.Cys175Ser (c.524G>C) pathogenic?

BMPR1A p.Cys175Ser (c.524G>C) is classified Uncertain significance in BMPR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-25). AlphaMissense: likely benign (0.1984); Very rare (popmax 0.000763%, nfe); Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Cys175Ser (c.524G>C)?

BMPR1A p.Cys175Ser (c.524G>C) is associated with juvenile polyposis syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.Cys175Ser (c.524G>C) in the general population?

BMPR1A p.Cys175Ser (c.524G>C) is very rare (popmax 0.000763%, nfe) (gnomAD).

How is Juvenile polyposis syndrome inherited?

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

What do computational predictors say about BMPR1A p.Cys175Ser (c.524G>C)?

AlphaMissense predicts likely benign (score 0.1984) — an in-silico prediction, not a clinical call.

BMPR1A p.Cys175Ser

c.524G>C · rs370091063 · VCV230207

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

juvenile polyposis syndrome

Computational evidence

Protein change
AlphaMissense	0.1984	likely benign
REVEL	0.415	indeterminate
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 27 kb · p 2.2e-08 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,908 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,144 alleles · very rare

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.Cys175Ser
Coding: c.524G>C
MANE Select: NM_004329
dbSNP: rs370091063
Type: single nucleotide variant
Location: chr10:86900120 (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: 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.Cys175Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
BMPR1A p.Cys175= Benign ★ 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-cys175ser (accessed [today's date]).

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