COL1A1 p.Pro403=
c.1209T>C · rs200786825 · VCV1650071
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, eas)
Conditions
2
Cardiovascular phenotype
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 0.51 | GERP -3.8, phastCons 0.77 |
| Overall | ||
| CADD | 12.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
East Asian · 17/44,836 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0198%
Overall
0.00155%
25/1,613,810 alleles · ultra-rare
exomes 22/1,461,792 · genomes 3/152,018 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0379% | 2,637 |
| South Asian | 0.0022% | 45,540 |
| Admixed American | 0.00167% | 59,996 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,494 |
| African / African-American | 0.00133% | 74,936 |
| European (non-Finnish) | 0.000254% | 393,304 |
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.Pro403=
- Coding
- c.1209T>C
- MANE Select
- NM_000088
- dbSNP
- rs200786825
- Type
- single nucleotide variant
- Location
- chr17:50195322 (GRCh38)
- Gene constraint
- LOEUF 0.159 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.26 · 14 PDB
- Residue 403
- the 'disordered' region; a modified residue (4-hydroxyproline); the 'triple-helical region' region
Similar variants
- COL1A1 p.Pro403Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-pro403 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown