C3 p.Ala739=
c.2217G>A · rs1042988644 · VCV2075256
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
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 -2.9 | GERP -3.5 |
| Overall | ||
| CADD | 3.976 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/59,976 alleles
Filtering AF
0.00544%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.000868%
14/1,612,800 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,568 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,820 |
| East Asian | 0.00223% | 44,804 |
| African / African-American | 0.00134% | 74,788 |
| South Asian | 0.0011% | 91,054 |
| European (non-Finnish) | 8.48e-05% | 1,179,842 |
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.Ala739=
- Coding
- c.2217G>A
- MANE Select
- NM_000064
- dbSNP
- rs1042988644
- Type
- single nucleotide variant
- Location
- chr19:6707104 (GRCh38)
- Gene constraint
- LOEUF 0.541 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.84 · 80 PDB
- Residue 739
- an α-helix; a disulfide bond
Similar variants
- C3 p.Ala739Val 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-ala739 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown