COL18A1 p.Pro993=
c.2979A>C · rs575364982 · VCV447124
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.44%, afr)
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 -5.8 | GERP -2.5 |
| Overall | ||
| CADD | 0.107 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.44%
African / African-American · 915/63,390 alleles
Filtering AF
1.37%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.33%
Overall
0.0829%
1,297/1,565,278 alleles · low-frequency
exomes 746/1,421,352 · genomes 551/143,926 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.44% | 69 |
| Middle Eastern | 0.327% | 306 |
| Remaining individualsnot grpmax-eligible | 0.154% | 649 |
| Admixed American | 0.113% | 888 |
| European (non-Finnish) | 0.0171% | 5,856 |
| South Asian | 0.00788% | 12,695 |
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
- COL18A1
- Protein
- p.Pro993=
- Coding
- c.2979A>C
- MANE Select
- NM_001379500
- dbSNP
- rs575364982
- Type
- single nucleotide variant
- Location
- chr21:45505244 (GRCh38)
- Gene constraint
- LOEUF 1.001 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.77 · 9 PDB
- Residue 993
- the 'triple-helical region 3 (col3)' region; the 'disordered' region
Similar variants
- COL18A1 p.Pro993Arg Uncertain significance ★ ⚠ same residue
- COL18A1 p.Pro993Ser Uncertain significance ★ ⚠ same residue
- COL18A1 c.1897-2A>G Likely pathogenic ★★ same type
- COL18A1 c.2157+1G>A Likely pathogenic ★★ same type
- COL18A1 c.2577+1G>A Pathogenic/Likely pathogenic ★★ same type
- COL18A1 c.3013+3A>C Likely pathogenic ★★ same type
- COL18A1 c.3809+2T>C Pathogenic ★★ same type
- COL18A1 c.798+1G>T Likely pathogenic ★★ 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/col18a1-p-pro993 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown