Is BMPR1A p.Ser501= (c.1503A>G) pathogenic?

BMPR1A p.Ser501= (c.1503A>G) is classified Likely benign in BMPR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-15). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BMPR1A p.Ser501= (c.1503A>G)?

BMPR1A p.Ser501= (c.1503A>G) is associated with hereditary neoplastic syndrome, juvenile polyposis syndrome (ClinVar).

How common is BMPR1A p.Ser501= (c.1503A>G) in the general population?

BMPR1A p.Ser501= (c.1503A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

BMPR1A p.Ser501=

c.1503A>G · rs1413602483 · VCV1531509

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.21	GERP -3.8, phastCons 0.25
Overall
CADD	5.499	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,904 alleles

Overall 0.000124% 2/1,614,114 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,904
European (non-Finnish)	8.47e-05%	1,180,043

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.Ser501=
Coding: c.1503A>G
MANE Select: NM_004329
dbSNP: rs1413602483
Type: single nucleotide variant
Location: chr10:86923623 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 501: the protein kinase domain

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.Ser501Ala Uncertain significance ★★ ⚠ same residue
BMPR1A p.Ser501Ter Pathogenic ★ same residue
BMPR1A p.Ser501Leu 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-ser501 (accessed [today's date]).

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