COL18A1 p.Pro52=
c.156G>A · rs373105258 · VCV1917481
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00559%, nfe)
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 -2.6 | GERP -3.4 |
| Overall | ||
| CADD | 1.355 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00559%
European (non-Finnish) · 66/1,180,038 alleles
Filtering AF
0.00451%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00411%
Overall
0.00459%
74/1,613,202 alleles · very rare
exomes 64/1,460,834 · genomes 10/152,368 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00559% | 17,879 |
| African / African-American | 0.00533% | 18,768 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,831 |
| South Asian | 0.0011% | 91,086 |
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.Pro52=
- Coding
- c.156G>A
- MANE Select
- NM_001379500
- dbSNP
- rs373105258
- Type
- single nucleotide variant
- Location
- chr21:45468291 (GRCh38)
- Gene constraint
- LOEUF 1.001 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.77 · 9 PDB
- Residue 52
- the 'disordered' region
Similar variants
- COL18A1 p.Pro52Gln Uncertain significance ★ ⚠ same residue
- COL18A1 p.Pro52Leu 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-pro52 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown