COL6A3 p.Arg1998=
c.5994A>C · rs757662895 · VCV3057752
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, sas)
Conditions
1
COL6A3-related disorder
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 -4.7 | GERP -2.5 |
| Overall | ||
| CADD | 0.945 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
South Asian · 16/91,074 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00888%
Overall
0.00297%
48/1,613,886 alleles · ultra-rare
exomes 47/1,461,882 · genomes 1/152,004 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0176% | 5,692 |
| European (non-Finnish) | 0.00263% | 38,065 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
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
- COL6A3
- Protein
- p.Arg1998=
- Coding
- c.5994A>C
- MANE Select
- NM_004369
- dbSNP
- rs757662895
- Type
- single nucleotide variant
- Location
- chr2:237363322 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI <0.01 (gnomAD)
- Residue 1998
- the vwfa 10 domain; the 'nonhelical region' region
Disease context
COL6A3-related disorder
Similar variants
- COL6A3 p.Arg1998Ter Pathogenic/Likely pathogenic ★★ same residue
- COL6A3 p.Arg1998Gln Uncertain significance ★★ same residue
- COL6A3 c.6354+1G>A Pathogenic/Likely pathogenic ★★ same condition
- COL6A3 p.Arg2202Ter Pathogenic/Likely pathogenic ★★ same condition
- COL6A3 p.Gln26Ter Pathogenic/Likely pathogenic ★★ same condition
- COL6A3 p.Gly2053Cys Pathogenic/Likely pathogenic ★★ same condition
- COL6A3 p.Gly2053Val Pathogenic ★★ same condition
- COL6A3 p.Gly2065Arg Pathogenic/Likely pathogenic ★★ same condition
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/col6a3-p-arg1998 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown