Is COL1A2 p.Val1290= (c.3870C>T) pathogenic?

COL1A2 p.Val1290= (c.3870C>T) is classified Conflicting classifications of pathogenicity in COL1A2 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-05-01). Ultra-rare (popmax 0.0164%, mid); Associated with osteogenesis imperfecta.

What condition is associated with COL1A2 p.Val1290= (c.3870C>T)?

COL1A2 p.Val1290= (c.3870C>T) is associated with osteogenesis imperfecta, osteogenesis imperfecta type 1, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL1A2 p.Val1290= (c.3870C>T) in the general population?

COL1A2 p.Val1290= (c.3870C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Osteogenesis imperfecta inherited?

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

COL1A2 p.Val1290=

c.3870C>T · rs926855674 · VCV912035

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

osteogenesis imperfecta

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 0.55	GERP -1.5, phastCons 0.95
Overall
CADD	8.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00713% 115/1,613,896 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0144%	6,942
Admixed American	0.00833%	11,998
European (non-Finnish)	0.00814%	12,291
South Asian	0.00439%	22,770

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: COL1A2
Protein: p.Val1290=
Coding: c.3870C>T
MANE Select: NM_000089
dbSNP: rs926855674
Type: single nucleotide variant
Location: chr7:94429346 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 1290: the fibrillar collagen nc1 domain; a disulfide bond

Full COL1A2 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 1 Ehlers-Danlos syndrome, classic type, 1 Ehlers-Danlos syndrome Ehlers-Danlos syndrome, arthrochalasia type, 2

For Osteogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

COL1A2 c.1197+5G>A Pathogenic ★★ same condition
COL1A2 c.1404+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A2 c.1503+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A2 c.1503+1G>C Pathogenic ★★ same condition
COL1A2 c.1557+3A>G Pathogenic ★★ same condition
COL1A2 c.2026-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL1A2 c.2133+6T>A Pathogenic ★★ same condition
COL1A2 c.226-2A>G Pathogenic/Likely pathogenic ★★ 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/col1a2-p-val1290 (accessed [today's date]).

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