C3 p.Pro1251=
c.3753C>T · rs2230209 · VCV1665735
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, sas)
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 -11 | GERP -3.8 |
| Overall | ||
| CADD | 0.084 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
South Asian · 16/91,078 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00888%
Overall
0.00904%
146/1,614,158 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0176% | 5,692 |
| Middle Eastern | 0.0165% | 6,058 |
| European (non-Finnish) | 0.0106% | 9,440 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,252 |
| Admixed American | 0.00167% | 60,022 |
| African / African-American | 0.00133% | 75,042 |
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.Pro1251=
- Coding
- c.3753C>T
- MANE Select
- NM_000064
- dbSNP
- rs2230209
- Type
- single nucleotide variant
- Location
- chr19:6686181 (GRCh38)
- Gene constraint
- LOEUF 0.541 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.84 · 80 PDB
- Residue 1251
- 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-pro1251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown