Is BMP1 p.Leu735= (c.2205C>G) pathogenic?

BMP1 p.Leu735= (c.2205C>G) is classified Benign in BMP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 11%, afr) — too common for a highly-penetrant pathogenic allele; Associated with osteogenesis imperfecta type 13.

What condition is associated with BMP1 p.Leu735= (c.2205C>G)?

BMP1 p.Leu735= (c.2205C>G) is associated with osteogenesis imperfecta type 13, osteogenesis imperfecta (ClinVar).

How is Osteogenesis imperfecta inherited?

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

BMP1 p.Leu735=

Q: How common is BMP1 p.Leu735= (c.2205C>G) in the general population?

BMP1 p.Leu735= (c.2205C>G) is common (popmax 11%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2205C>G · rs28710878 · VCV362593

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 11%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

osteogenesis imperfecta type 13

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 -1.2	GERP -5.3
Overall
CADD	2.951	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11% African / African-American · 8,276/75,056 alleles

Filtering AF 10.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.7%

Overall 0.574% 9,259/1,613,802 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11%	9
Remaining individualsnot grpmax-eligible	0.726%	138
Admixed American	0.672%	149
Middle Eastern	0.347%	289
South Asian	0.0275%	3,641
European (non-Finnish)	0.00678%	14,749

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.Leu735=
Coding: c.2205C>G
MANE Select: NM_006129
dbSNP: rs28710878
Type: single nucleotide variant
Location: chr8:22201900 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 735: a disulfide bond; the egf-like 2; calcium-binding domain

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

Disease context

osteogenesis imperfecta type 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: osteogenesis imperfecta

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.Cys183Ter Pathogenic/Likely pathogenic ★★ same condition
BMP1 c.*452A>C Uncertain significance ★★ same condition
BMP1 p.Arg152Gln Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg393Gln Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg395Leu Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg411His Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg417Cys Uncertain significance ★★ same condition
BMP1 p.Arg562Trp Uncertain significance ★★ ⚠ 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-leu735 (accessed [today's date]).

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