C6 p.Arg289=
c.867A>G · rs1457405276 · VCV3053599
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
1
C6-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 -0.091 | GERP -0.91 |
| Overall | ||
| CADD | 2.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,984 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000372%
6/1,613,718 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,992 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
| European (non-Finnish) | 0.000254% | 393,286 |
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
- C6
- Protein
- p.Arg289=
- Coding
- c.867A>G
- MANE Select
- NM_000065
- dbSNP
- rs1457405276
- Type
- single nucleotide variant
- Location
- chr5:41181419 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.72 · 11 PDB
- Residue 289
- a turn; the macpf domain
Disease context
C6-related disorder
Similar variants
- C6 p.Gln268Ter Likely pathogenic ★ same condition
- C6 c.-3G>A Likely benign same condition
- C6 p.Asp627fs Likely pathogenic ★★ same condition
- C6 p.Ser813fs Pathogenic/Likely pathogenic ★★ same condition
- C6 p.Gln111fs Likely pathogenic ★ same condition
- C6 p.Arg596Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Arg606Ter Pathogenic ★★ same type
- C6 p.Cys218Ter 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/c6-p-arg289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown