COL18A1 p.Asp323=
c.969C>T · rs781489276 · VCV1387488
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, 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 -9.4 | GERP -2.5 |
| Overall | ||
| CADD | 5.295 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
African / African-American · 10/74,892 alleles
Filtering AF
0.00723%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0055%
Overall
0.00248%
40/1,612,716 alleles · ultra-rare
exomes 32/1,460,526 · genomes 8/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0134% | 7,489 |
| Admixed American | 0.0117% | 8,556 |
| South Asian | 0.00331% | 30,243 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,207 |
| East Asian | 0.00223% | 44,850 |
| European (non-Finnish) | 0.00144% | 69,384 |
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.Asp323=
- Coding
- c.969C>T
- MANE Select
- NM_001379500
- dbSNP
- rs781489276
- Type
- single nucleotide variant
- Location
- chr21:45477451 (GRCh38)
- Gene constraint
- LOEUF 1.001 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.77 · 9 PDB
Similar variants
- 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
- COL18A1 c.929-2A>G 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-asp323 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown