C3 p.Asp1096=
c.3288C>T · rs780264809 · VCV757460
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00585%, 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 0.69 | GERP 1.7, phastCons 0.092 |
| Overall | ||
| CADD | 8.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00585%
European (non-Finnish) · 69/1,180,032 alleles
Filtering AF
0.0047%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00431%
Overall
0.0044%
71/1,614,046 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00585% | 17,102 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00133% | 74,928 |
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.Asp1096=
- Coding
- c.3288C>T
- MANE Select
- NM_000064
- dbSNP
- rs780264809
- Type
- single nucleotide variant
- Location
- chr19:6693026 (GRCh38)
- Gene constraint
- LOEUF 0.541 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.84 · 80 PDB
- Residue 1096
- an α-helix; a disulfide bond
Similar variants
- 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
- C3 p.Ile1157Thr 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-asp1096 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown