Is BMPR1A p.Ser39= (c.117C>G) pathogenic?

BMPR1A p.Ser39= (c.117C>G) is classified Benign/Likely benign in BMPR1A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-31). Very rare (popmax 0.00534%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BMPR1A p.Ser39= (c.117C>G)?

BMPR1A p.Ser39= (c.117C>G) is associated with hereditary neoplastic syndrome, pulmonary arterial hypertension, juvenile polyposis syndrome (ClinVar).

How common is BMPR1A p.Ser39= (c.117C>G) in the general population?

BMPR1A p.Ser39= (c.117C>G) is very rare (popmax 0.00534%, afr) (gnomAD).

BMPR1A p.Ser39=

c.117C>G · rs757333646 · VCV239853

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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 -6.7	GERP -5.2
Overall
CADD	1.561	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,894 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00273% 44/1,613,722 alleles · very rare exomes 40/1,461,578 · genomes 4/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,724
European (non-Finnish)	0.00339%	29,500

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.Ser39=
Coding: c.117C>G
MANE Select: NM_004329
dbSNP: rs757333646
Type: single nucleotide variant
Location: chr10:86890111 (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: pulmonary arterial hypertension juvenile polyposis syndrome

Similar variants

BMPR1A p.Ser39Cys Uncertain significance ★★ ⚠ same residue
BMPR1A p.Ser39Phe Uncertain significance ★★ ⚠ same residue
BMPR1A p.Ser39Tyr 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-ser39 (accessed [today's date]).

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