C6 p.Leu766=
c.2296C>T · rs374161182 · VCV1558897
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0846%, nfe)
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 0.38 | GERP -1.6 |
| Overall | ||
| CADD | 1.168 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0846%
European (non-Finnish) · 993/1,173,372 alleles
Filtering AF
0.0802%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0785%
Overall
0.0663%
1,065/1,606,464 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0846% | 1,182 |
| Finnishnot grpmax-eligible | 0.0469% | 2,132 |
| Remaining individualsnot grpmax-eligible | 0.037% | 2,704 |
| Admixed American | 0.0183% | 5,451 |
| African / African-American | 0.00937% | 10,676 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,554 |
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.Leu766=
- Coding
- c.2296C>T
- MANE Select
- NM_000065
- dbSNP
- rs374161182
- Type
- single nucleotide variant
- Location
- chr5:41150020 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.72 · 11 PDB
- Residue 766
- the 'c5b-binding domain' region; the 'factor i module (fim) 1' region
Similar variants
- C6 p.Arg596Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Arg606Ter Pathogenic ★★ same type
- C6 p.Cys218Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Tyr683Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Ala21Val Uncertain significance ★★ ⚠ same type
- C6 p.Ala396Gly Uncertain significance ★★ ⚠ same type
- C6 p.Ala456Thr Uncertain significance ★★ ⚠ same type
- C6 p.Ala500Ser Uncertain significance ★★ ⚠ 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-leu766 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown