C6 p.Lys706=
c.2118G>A · rs375320778 · VCV1534189
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.11 | GERP -0.24, phastCons 0.92 |
| Overall | ||
| CADD | 3.737 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.165%
Middle Eastern · 10/6,064 alleles
Filtering AF
0.0895%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.068%
Overall
0.0228%
368/1,613,594 alleles · rare
exomes 331/1,461,384 · genomes 37/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.165% | 606 |
| Remaining individualsnot grpmax-eligible | 0.0384% | 2,602 |
| European (non-Finnish) | 0.0266% | 3,757 |
| Admixed American | 0.02% | 4,998 |
| African / African-American | 0.00934% | 10,704 |
| South Asian | 0.0011% | 91,076 |
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.Lys706=
- Coding
- c.2118G>A
- MANE Select
- NM_000065
- dbSNP
- rs375320778
- Type
- single nucleotide variant
- Location
- chr5:41153982 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.72 · 11 PDB
- Residue 706
- the sushi 2 domain; the 'c5b-binding domain' region; an α-helix; the 'ccp 2' 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-lys706 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown