C1R p.Arg463=
c.1389C>T · VCV3768295
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0746%, afr)
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 0.091 | GERP -3.7, phastCons 0.63 |
| Overall | ||
| CADD | 3.532 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0746%
African / African-American · 56/75,034 alleles
Filtering AF
0.0589%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0533%
Overall
0.00459%
74/1,612,498 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0746% | 1,340 |
| Middle Eastern | 0.033% | 3,030 |
| Admixed American | 0.00502% | 19,913 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,814 |
| South Asian | 0.0011% | 90,774 |
| European (non-Finnish) | 0.000763% | 131,025 |
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.Arg463=
- Coding
- c.1389C>T
- MANE Select
- NM_001733
- Type
- single nucleotide variant
- Location
- chr12:7081261 (GRCh38)
- Gene constraint
- LOEUF 0.635 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 87.33 · 12 PDB
- Residue 463
- a functional site (cleavage; by autolysis); a disulfide bond
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-arg463 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown