COL18A1 p.Asp398=
c.1194C>T · rs370965213 · VCV2069391
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0191%, eas)
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 -8.3 | GERP -2.2 |
| Overall | ||
| CADD | 2.578 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0191%
East Asian · 8/41,836 alleles
Filtering AF
0.00949%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00691%
Overall
0.00475%
74/1,556,510 alleles · ultra-rare
exomes 68/1,404,198 · genomes 6/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0191% | 5,229 |
| Admixed American | 0.00559% | 17,893 |
| Remaining individualsnot grpmax-eligible | 0.00497% | 20,122 |
| European (non-Finnish) | 0.00497% | 20,134 |
| African / African-American | 0.00272% | 36,784 |
| South Asian | 0.00117% | 85,248 |
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.Asp398=
- Coding
- c.1194C>T
- MANE Select
- NM_001379500
- dbSNP
- rs370965213
- Type
- single nucleotide variant
- Location
- chr21:45477938 (GRCh38)
- Gene constraint
- LOEUF 1.001 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.77 · 9 PDB
- Residue 398
- the fz domain
Similar variants
- COL18A1 p.Asp398Val 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
- COL18A1 c.928+2T>C 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-asp398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown