Is BMP1 p.Phe808= (c.2424C>T) pathogenic?

BMP1 p.Phe808= (c.2424C>T) is classified Conflicting classifications of pathogenicity in BMP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-29). Very rare (popmax 0.00223%, eas); Associated with osteogenesis imperfecta type 13.

What condition is associated with BMP1 p.Phe808= (c.2424C>T)?

BMP1 p.Phe808= (c.2424C>T) is associated with osteogenesis imperfecta type 13 (ClinVar).

How common is BMP1 p.Phe808= (c.2424C>T) in the general population?

BMP1 p.Phe808= (c.2424C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Osteogenesis imperfecta inherited?

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

BMP1 p.Phe808=

c.2424C>T · rs761259265 · VCV2885627

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -15	GERP -5.3
Overall
CADD	0.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000684% 10/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000678%	147,504

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.Phe808=
Coding: c.2424C>T
MANE Select: NM_006129
dbSNP: rs761259265
Type: single nucleotide variant
Location: chr8:22207365 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 808: a disulfide bond; the cub 4 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

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.Arg417Cys Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg562Trp Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg628His 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-phe808 (accessed [today's date]).

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