COL28A1 p.Pro449=
c.1347T>C · rs191967922 · VCV2657315
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.148%, mid)
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 -4.5 | GERP -4.9 |
| Overall | ||
| CADD | 0.427 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.148%
Middle Eastern · 9/6,062 alleles
Filtering AF
0.113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.105%
Overall
0.0125%
201/1,613,918 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.148% | 674 |
| African / African-American | 0.135% | 743 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,976 |
| Admixed American | 0.0317% | 3,159 |
| European (non-Finnish) | 0.00407% | 24,581 |
| South Asian | 0.00329% | 30,353 |
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
- COL28A1
- Protein
- p.Pro449=
- Coding
- c.1347T>C
- MANE Select
- NM_001037763
- dbSNP
- rs191967922
- Type
- single nucleotide variant
- Location
- chr7:7456068 (GRCh38)
- Gene constraint
- LOEUF 1.124 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.81
- Residue 449
- the 'disordered' region
Similar variants
- COL28A1 p.Pro449Thr Uncertain significance ★ ⚠ same residue
- COL28A1 c.1792-2A>G Uncertain significance ★ same type
- COL28A1 p.Ala1075Asp Uncertain significance ★ ⚠ same type
- COL28A1 p.Ala274Thr Uncertain significance ★ ⚠ same type
- COL28A1 p.Ala535Gly Uncertain significance ★ ⚠ same type
- COL28A1 p.Ala631Asp Uncertain significance ★ ⚠ same type
- COL28A1 p.Ala825Val Uncertain significance ★ ⚠ same type
- COL28A1 p.Ala864Ser Uncertain significance ★ ⚠ same type
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/col28a1-p-pro449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown