Is BMP1 p.Ala623Val (c.1868C>T) pathogenic?

BMP1 p.Ala623Val (c.1868C>T) is classified Uncertain significance in BMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely pathogenic (0.966); Very rare (popmax 0.00892%, eas); Associated with osteogenesis imperfecta type 13.

What condition is associated with BMP1 p.Ala623Val (c.1868C>T)?

BMP1 p.Ala623Val (c.1868C>T) is associated with osteogenesis imperfecta type 13 (ClinVar).

How common is BMP1 p.Ala623Val (c.1868C>T) in the general population?

BMP1 p.Ala623Val (c.1868C>T) is very rare (popmax 0.00892%, eas) (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.Ala623Val (c.1868C>T)?

AlphaMissense predicts likely pathogenic (score 0.966) — an in-silico prediction, not a clinical call.

BMP1 p.Ala623Val

c.1868C>T · rs752330967 · VCV910375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

osteogenesis imperfecta type 13

Computational evidence

Protein change
AlphaMissense	0.966	likely pathogenic
REVEL	0.317	indeterminate
SaProt	LLR -8.25	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	25.5	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 0.00892% East Asian · 4/44,846 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000479% 7/1,461,850 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,212
Admixed American	0.005%	20,005

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.Ala623Val
Coding: c.1868C>T
MANE Select: NM_006129
dbSNP: rs752330967
Type: single nucleotide variant
Location: chr8:22196782 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 623: the cub 3 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-ala623val (accessed [today's date]).

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