C3 p.Cys694=
c.2082C>T · VCV3605752
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, 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 -5.2 | GERP -3.5 |
| Overall | ||
| CADD | 0.307 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
European (non-Finnish) · 13/1,179,446 alleles
Filtering AF
0.000615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.000806%
13/1,612,694 alleles · very rare
exomes 13/1,460,498 · genomes 0/152,196 · joint denominator
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
- C3
- Protein
- p.Cys694=
- Coding
- c.2082C>T
- MANE Select
- NM_000064
- Type
- single nucleotide variant
- Location
- chr19:6707239 (GRCh38)
- Gene constraint
- LOEUF 0.541 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.84 · 80 PDB
- Residue 694
- the anaphylatoxin-like domain; an α-helix; a disulfide bond
Similar variants
- C3 p.Cys694Phe Uncertain significance ★ ⚠ same residue
- C3 c.1003+1G>A Pathogenic/Likely pathogenic ★★ same type
- C3 c.2863+1G>T Likely pathogenic ★★ same type
- C3 c.4030-2A>G Likely pathogenic ★★ same type
- C3 p.Arg161Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- C3 p.Arg592Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- C3 p.Arg592Trp Likely pathogenic ★★ ⚠ same type
- C3 p.Arg764Ter 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/c3-p-cys694 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown