COL1A1 p.Pro149=
c.447T>C · VCV3631081
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00271%, sas)
Conditions
1
osteogenesis imperfecta type 1
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 -0.42 | GERP -2.1, phastCons 0.001 |
| Overall | ||
| CADD | 10.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00271%
South Asian · 2/73,852 alleles
Filtering AF
0.000449%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000168%
Overall
0.000303%
4/1,321,192 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00271% | 36,926 |
| African / African-American | 0.00142% | 70,188 |
| European (non-Finnish) | 9.04e-05% | 1,105,959 |
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
- COL1A1
- Protein
- p.Pro149=
- Coding
- c.447T>C
- MANE Select
- NM_000088
- Type
- single nucleotide variant
- Location
- chr17:50199250 (GRCh38)
- Gene constraint
- LOEUF 0.159 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.26 · 14 PDB
- Residue 149
- an α-helix; the 'disordered' region
Similar variants
- COL1A1 c.1003-1G>A Pathogenic/Likely pathogenic ★★ same condition
- COL1A1 c.103+1G>A Pathogenic/Likely pathogenic ★★ same condition
- COL1A1 c.103+2T>C Pathogenic ★★ same condition
- COL1A1 c.104-1G>T Pathogenic/Likely pathogenic ★★ same condition
- COL1A1 c.104-2A>G Pathogenic/Likely pathogenic ★★ same condition
- COL1A1 c.1056+1G>A Pathogenic ★★ same condition
- COL1A1 c.1057-1G>A Pathogenic ★★ same condition
- COL1A1 c.1057-2A>C 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/col1a1-p-pro149 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown