C1S p.Ala307=
c.921G>A · rs782012840 · VCV798285
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.35 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 5.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00362%
Overall
0.0044%
71/1,613,932 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| South Asian | 0.00659% | 15,181 |
| European (non-Finnish) | 0.00509% | 19,665 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
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.Ala307=
- Coding
- c.921G>A
- MANE Select
- NM_001734
- dbSNP
- rs782012840
- Type
- single nucleotide variant
- Location
- chr12:7066567 (GRCh38)
- Gene constraint
- LOEUF 0.783 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.02 · 14 PDB
- Residue 307
- a disulfide bond; the sushi 1 domain
Similar variants
- C1S p.Ala307Val Benign/Likely benign ★★ 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-ala307 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown