Is BMP1 p.Glu239= (c.717G>A) pathogenic?

BMP1 p.Glu239= (c.717G>A) is classified Conflicting classifications of pathogenicity in BMP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-17). Ultra-rare (popmax 0.0468%, afr); Associated with osteogenesis imperfecta.

What condition is associated with BMP1 p.Glu239= (c.717G>A)?

BMP1 p.Glu239= (c.717G>A) is associated with osteogenesis imperfecta (ClinVar).

How common is BMP1 p.Glu239= (c.717G>A) in the general population?

BMP1 p.Glu239= (c.717G>A) is ultra-rare (popmax 0.0468%, afr) (gnomAD).

How is Osteogenesis imperfecta inherited?

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

BMP1 p.Glu239=

c.717G>A · rs149856199 · VCV1702088

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, afr)

Conditions

osteogenesis imperfecta

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 3.5	GERP -2.4, phastCons 1
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0468% African / African-American · 35/74,764 alleles

Filtering AF 0.0346% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0303%

Overall 0.00336% 54/1,607,282 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0468%	2,136
Admixed American	0.00336%	29,802
Remaining individualsnot grpmax-eligible	0.00322%	31,040
European (non-Finnish)	0.00128%	78,402

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: BMP1
Protein: p.Glu239=
Coding: c.717G>A
MANE Select: NM_006129
dbSNP: rs149856199
Type: single nucleotide variant
Location: chr8:22177126 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 239: a disulfide bond; the peptidase m12a domain; an α-helix

Full BMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Osteogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

BMP1 p.Arg411His Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg76Trp Uncertain significance ★★ ⚠ same condition
BMP1 p.Pro816Ala Uncertain significance ★★ ⚠ same condition
BMP1 p.Ser692Phe Uncertain significance ★★ ⚠ same condition
BMP1 c.1766-5C>T Benign ★★ same condition
BMP1 p.Arg314His Benign/Likely benign ★★ ⚠ same condition
BMP1 p.Arg371His Benign/Likely benign ★★ ⚠ same condition
BMP1 p.Asp705= Benign ★★ 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/bmp1-p-glu239 (accessed [today's date]).

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