C1S p.Ala463=
c.1389G>A · rs782139172 · VCV1657228
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, 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 -3.6 |
| Overall | ||
| CADD | 7.691 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,084 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000684%
10/1,461,870 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,217 |
| Admixed American | 0.005% | 20,011 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| European (non-Finnish) | 8.47e-05% | 1,180,013 |
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
- C1S
- Protein
- p.Ala463=
- Coding
- c.1389G>A
- MANE Select
- NM_001734
- dbSNP
- rs782139172
- Type
- single nucleotide variant
- Location
- chr12:7069973 (GRCh38)
- Gene constraint
- LOEUF 0.783 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.02 · 14 PDB
- Residue 463
- a β-strand; a disulfide bond; the peptidase s1 domain
Similar variants
- C1S p.Ala463Val Uncertain significance ★ ⚠ same residue
- C1S p.Arg523Ter Pathogenic ★★ same type
- C1S c.1196-3C>T Uncertain significance ★★ same type
- C1S c.717+5G>A Uncertain significance ★★ same type
- C1S c.717+6T>A Uncertain significance ★★ same type
- C1S p.Ala227Val Uncertain significance ★★ ⚠ same type
- C1S p.Ala231Val Uncertain significance ★★ ⚠ same type
- C1S p.Ala584Val 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/c1s-p-ala463 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown