C6 p.Leu883=
c.2649A>G · rs754612623 · VCV2997731
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.45 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.5 | GERP -3.3 |
| Overall | ||
| CADD | 0.464 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,854 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000684%
10/1,461,328 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,854 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| European (non-Finnish) | 0.000678% | 147,452 |
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.Leu883=
- Coding
- c.2649A>G
- MANE Select
- NM_000065
- dbSNP
- rs754612623
- Type
- single nucleotide variant
- Location
- chr5:41142981 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.72 · 11 PDB
- Residue 883
- the kazal-like 2 domain; the 'c5b-binding domain' region; the 'factor i module (fim) 2' region; a disulfide bond
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-leu883 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown