Is BMPR1A p.Arg511Ser (c.1533A>C) pathogenic?

BMPR1A p.Arg511Ser (c.1533A>C) is classified Uncertain significance in BMPR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-03-02). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Arg511Ser (c.1533A>C)?

BMPR1A p.Arg511Ser (c.1533A>C) is associated with juvenile polyposis syndrome (ClinVar).

How common is BMPR1A p.Arg511Ser (c.1533A>C) in the general population?

BMPR1A p.Arg511Ser (c.1533A>C) is absent from gnomAD v4.1 (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.Arg511Ser (c.1533A>C)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

BMPR1A p.Arg511Ser

c.1533A>C · rs730881437 · VCV182071

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

juvenile polyposis syndrome

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 2% in BMPR1A
REVEL	0.901	moderately pathogenic-leaning
SaProt	LLR -14.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -2.5, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 4,412 bp · p 2.1e-15 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMPR1A
Protein: p.Arg511Ser
Coding: c.1533A>C
MANE Select: NM_004329
dbSNP: rs730881437
Type: single nucleotide variant
Location: chr10:86923653 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 511: 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

For Juvenile polyposis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

BMPR1A p.Arg511Thr 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-arg511ser (accessed [today's date]).

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