Is BMP1 p.Ala590= (c.1770T>C) pathogenic?

BMP1 p.Ala590= (c.1770T>C) is classified Benign in BMP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 20%, eas) — too common for a highly-penetrant pathogenic allele; Associated with osteogenesis imperfecta type 13.

What condition is associated with BMP1 p.Ala590= (c.1770T>C)?

BMP1 p.Ala590= (c.1770T>C) is associated with osteogenesis imperfecta type 13 (ClinVar).

How is Osteogenesis imperfecta inherited?

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

BMP1 p.Ala590=

Q: How common is BMP1 p.Ala590= (c.1770T>C) in the general population?

BMP1 p.Ala590= (c.1770T>C) is common (popmax 20%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1770T>C · rs2229777 · VCV362589

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 20%, eas) — 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 2.8	GERP 0.47, phastCons 1
Overall
CADD	12.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20% East Asian · 8,980/44,820 alleles

Filtering AF 19.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.5%

Overall 11.4% 184,150/1,613,668 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	20%	5
Finnishnot grpmax-eligible	14.9%	7
Middle Eastern	14.2%	7
South Asian	13.3%	7
Remaining individualsnot grpmax-eligible	11.5%	9
African / African-American	11.2%	9
European (non-Finnish)	11%	9
Amishnot grpmax-eligible	11%	9
Admixed American	7.72%	13
Ashkenazi Jewishnot grpmax-eligible	6.99%	14

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.Ala590=
Coding: c.1770T>C
MANE Select: NM_006129
dbSNP: rs2229777
Type: single nucleotide variant
Location: chr8:22196684 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB

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-ala590 (accessed [today's date]).

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