C1R p.Ala559=
c.1677C>T · VCV4281074
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0132%, 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 1.5 | GERP 0.79, phastCons 1 |
| Overall | ||
| CADD | 10.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0132%
South Asian · 12/91,092 alleles
Filtering AF
0.0075%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.00428%
69/1,613,630 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0132% | 7,591 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,817 |
| European (non-Finnish) | 0.00458% | 21,846 |
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
- C1R
- Protein
- p.Ala559=
- Coding
- c.1677C>T
- MANE Select
- NM_001733
- Type
- single nucleotide variant
- Location
- chr12:7080973 (GRCh38)
- Gene constraint
- LOEUF 0.635 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 87.33 · 12 PDB
- Residue 559
- a β-strand; a disulfide bond; the peptidase s1 domain
Similar variants
- C1R p.Arg301Pro Pathogenic ★★ ⚠ same type
- C1R p.Asp290Gly Pathogenic/Likely pathogenic ★★ same type
- C1R p.Cys338Arg Pathogenic ★★ same type
- C1R p.Cys371Trp Pathogenic ★★ same type
- C1R p.Gly297Asp Pathogenic/Likely pathogenic ★★ same type
- C1R p.His642Gln Uncertain significance ★★ ⚠ same type
- C1R p.Leu285Met Uncertain significance ★★ ⚠ same type
- C1R p.Phe318Cys Uncertain significance ★★ ⚠ 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/c1r-p-ala559 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown