COL1A1 p.Pro604=
c.1812T>C · rs151328660 · VCV508831
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0679%, afr)
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 -0.8 | GERP -3.5 |
| Overall | ||
| CADD | 5.485 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0679%
African / African-American · 51/75,056 alleles
Filtering AF
0.0531%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0478%
Overall
0.00322%
52/1,614,134 alleles · ultra-rare
exomes 26/1,461,814 · genomes 26/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0679% | 1,472 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,508 |
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.Pro604=
- Coding
- c.1812T>C
- MANE Select
- NM_000088
- dbSNP
- rs151328660
- Type
- single nucleotide variant
- Location
- chr17:50193003 (GRCh38)
- Gene constraint
- LOEUF 0.159 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.26 · 14 PDB
- Residue 604
- the 'disordered' region; the 'triple-helical region' region; a modified residue (4-hydroxyproline)
Similar variants
- COL1A1 p.Pro604Ala Uncertain significance ★★ ⚠ same residue
- COL1A1 p.Pro604His Conflicting classifications of pathogenicity ★ ⚠ same residue
- COL1A1 p.Pro604Leu Uncertain significance ★ ⚠ same residue
- COL1A1 p.Pro604fs Pathogenic/Likely pathogenic ★★ 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
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-pro604 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown