Is BMP1 p.Ser692Phe (c.2075C>T) pathogenic?

BMP1 p.Ser692Phe (c.2075C>T) is classified Uncertain significance in BMP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-10-17). AlphaMissense: likely pathogenic (0.8357); Ultra-rare (popmax 0.0587%, nfe); Associated with osteogenesis imperfecta.

What condition is associated with BMP1 p.Ser692Phe (c.2075C>T)?

BMP1 p.Ser692Phe (c.2075C>T) is associated with osteogenesis imperfecta, osteogenesis imperfecta type 13 (ClinVar).

How common is BMP1 p.Ser692Phe (c.2075C>T) in the general population?

BMP1 p.Ser692Phe (c.2075C>T) is ultra-rare (popmax 0.0587%, nfe) (gnomAD).

How is Osteogenesis imperfecta inherited?

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

What do computational predictors say about BMP1 p.Ser692Phe (c.2075C>T)?

AlphaMissense predicts likely pathogenic (score 0.8357) — an in-silico prediction, not a clinical call.

BMP1 p.Ser692Phe

c.2075C>T · rs201303856 · VCV362590

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.8357 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0587%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

osteogenesis imperfecta

Computational evidence

Protein change
AlphaMissense	0.8357	likely pathogenic
REVEL	0.518	indeterminate
SaProt	LLR -9.96	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 35 kb · p 1e-07 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0587% European (non-Finnish) · 691/1,178,132 alleles

Filtering AF 0.055% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0536%

Overall 0.0455% 733/1,611,602 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0587%	1,705
Finnishnot grpmax-eligible	0.0328%	3,048
Remaining individualsnot grpmax-eligible	0.0224%	4,456
African / African-American	0.00668%	14,966
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,570
Admixed American	0.00167%	59,888

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.Ser692Phe
Coding: c.2075C>T
MANE Select: NM_006129
dbSNP: rs201303856
Type: single nucleotide variant
Location: chr8:22197388 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 692: the cub 3 domain

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

Also linked: osteogenesis imperfecta type 13

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-ser692phe (accessed [today's date]).

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