Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 11 submitters
gnomAD v4.1
Common
common (popmax 92.7%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
5
atypical hemolytic-uremic syndrome with C3 anomaly
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 -9.9 | GERP -3.5 |
| Overall | ||
| CADD | 0.068 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
92.7%
East Asian · 41,603/44,862 alleles
Filtering AF
92%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 91.7%
Overall
76.8%
1,239,780/1,613,598 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 92.7% | 1 |
| Admixed American | 87.6% | 1 |
| South Asian | 80.8% | 1 |
| Middle Eastern | 79.8% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 79.7% | 1 |
| Remaining individualsnot grpmax-eligible | 77.9% | 1 |
| African / African-American | 76% | 1 |
| Finnishnot grpmax-eligible | 75.5% | 1 |
| European (non-Finnish) | 75.4% | 1 |
| Amishnot grpmax-eligible | 61% | 2 |
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.Ala915=
- Coding
- c.2745T>C
- MANE Select
- NM_000064
- dbSNP
- rs423490
- Type
- single nucleotide variant
- Location
- chr19:6697395 (GRCh38)
- Gene constraint
- LOEUF 0.541 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.84 · 80 PDB
- Residue 915
- a β-strand; a disulfide bond
Similar variants
- C3 c.1003+1G>A Pathogenic/Likely pathogenic ★★ same condition
- C3 c.2863+1G>T Likely pathogenic ★★ same condition
- C3 c.4030-2A>G Likely pathogenic ★★ same condition
- C3 p.Arg161Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- C3 p.Arg592Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- C3 p.Arg592Trp Likely pathogenic ★★ ⚠ same condition
- C3 p.Arg764Ter Pathogenic/Likely pathogenic ★★ same condition
- C3 p.Ile1157Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
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-ala915 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown