COL18A1 p.Pro706=
c.2118C>T · rs768113816 · VCV2171989
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0667%, amr)
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 -15 | GERP -2.7 |
| Overall | ||
| CADD | 0.386 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0667%
Admixed American · 40/59,970 alleles
Filtering AF
0.0503%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0446%
Overall
0.00763%
123/1,612,090 alleles · ultra-rare
exomes 80/1,459,928 · genomes 43/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0667% | 1,499 |
| Middle Eastern | 0.0165% | 6,078 |
| African / African-American | 0.012% | 8,324 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,482 |
| European (non-Finnish) | 0.00551% | 18,148 |
| East Asian | 0.00223% | 44,880 |
| South Asian | 0.0022% | 45,527 |
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.Pro706=
- Coding
- c.2118C>T
- MANE Select
- NM_001379500
- dbSNP
- rs768113816
- Type
- single nucleotide variant
- Location
- chr21:45491275 (GRCh38)
- Gene constraint
- LOEUF 1.001 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.77 · 9 PDB
- Residue 706
- the 'disordered' region; the 'nonhelical region 1 (nc1)' region
Similar variants
- COL18A1 p.Pro706Thr Uncertain significance ★★ ⚠ same residue
- COL18A1 p.Pro706Arg Benign/Likely benign ★★ same residue
- COL18A1 p.Pro706Ala Uncertain significance ★ ⚠ same residue
- COL18A1 p.Pro706Leu Uncertain significance ★ ⚠ same residue
- COL18A1 p.Pro706Ser 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
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-pro706 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown