COL18A1 p.Asp418=
c.1254C>T · rs368594049 · VCV447111
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.358%, 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 -0.012 | GERP -2.2, phastCons 0.001 |
| Overall | ||
| CADD | 1.221 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.358%
African / African-American · 268/74,934 alleles
Filtering AF
0.322%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.309%
Overall
0.0183%
296/1,613,670 alleles · rare
exomes 130/1,461,598 · genomes 166/152,072 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.358% | 280 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
| Admixed American | 0.0183% | 5,456 |
| Middle Eastern | 0.0165% | 6,058 |
| European (non-Finnish) | 8.47e-05% | 1,179,954 |
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.Asp418=
- Coding
- c.1254C>T
- MANE Select
- NM_001379500
- dbSNP
- rs368594049
- Type
- single nucleotide variant
- Location
- chr21:45479907 (GRCh38)
- Gene constraint
- LOEUF 1.001 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.77 · 9 PDB
- Residue 418
- the fz domain
Similar variants
- COL18A1 p.Asp418Ala Uncertain significance ★★ ⚠ same residue
- COL18A1 p.Asp418Asn 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-asp418 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown