COL18A1 p.Ser557=
c.1671C>T · rs777320347 · VCV1416134
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
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 -0.035 | GERP -1.1, phastCons 0.001 |
| Overall | ||
| CADD | 5.601 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,082 alleles
Filtering AF
0.00741%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00693%
Overall
0.00794%
128/1,612,648 alleles · ultra-rare
exomes 113/1,460,414 · genomes 15/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,041 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,161 |
| European (non-Finnish) | 0.00882% | 11,336 |
| Admixed American | 0.00834% | 11,993 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,572 |
| African / African-American | 0.00133% | 74,912 |
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.Ser557=
- Coding
- c.1671C>T
- MANE Select
- NM_001379500
- dbSNP
- rs777320347
- Type
- single nucleotide variant
- Location
- chr21:45482022 (GRCh38)
- Gene constraint
- LOEUF 1.001 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.77 · 9 PDB
- Residue 557
- the laminin g-like domain
Similar variants
- COL18A1 p.Ser557Asn 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-ser557 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown