Is BMP1 p.Ala433Ser (c.1297G>T) pathogenic?

BMP1 p.Ala433Ser (c.1297G>T) is classified Pathogenic in BMP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-03-29). AlphaMissense: ambiguous (0.3494); Absent from gnomAD v4.1; Associated with osteogenesis imperfecta type 13.

What condition is associated with BMP1 p.Ala433Ser (c.1297G>T)?

BMP1 p.Ala433Ser (c.1297G>T) is associated with osteogenesis imperfecta type 13 (ClinVar).

How common is BMP1 p.Ala433Ser (c.1297G>T) in the general population?

BMP1 p.Ala433Ser (c.1297G>T) is absent from gnomAD v4.1 (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.Ala433Ser (c.1297G>T)?

AlphaMissense predicts ambiguous (score 0.3494) — an in-silico prediction, not a clinical call.

BMP1 p.Ala433Ser

c.1297G>T · rs786205220 · VCV190234

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3494 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

osteogenesis imperfecta type 13

Computational evidence

Protein change
AlphaMissense	0.3494	ambiguous
REVEL	0.231	benign-leaning
SaProt	LLR -9.45	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.91	donor loss · deltas
Pangolin	Δ0.80	loss · gain 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 35 kb · p 1e-07 · regional, not allelic
Overall
CADD	34.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMP1
Protein: p.Ala433Ser
Coding: c.1297G>T
MANE Select: NM_006129
dbSNP: rs786205220
Type: single nucleotide variant
Location: chr8:22194174 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 433: the cub 1 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-ala433ser (accessed [today's date]).

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