Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 16.7%, mid) — too common for a highly-penetrant pathogenic allele
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 2.2 | GERP 0.87, phastCons 1 |
| Overall | ||
| CADD | 12.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
16.7%
Middle Eastern · 1,009/6,060 alleles
Filtering AF
15.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 15.5%
Overall
7.72%
124,652/1,613,732 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 16.7% | 6 |
| African / African-American | 14.9% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 13.7% | 7 |
| Amishnot grpmax-eligible | 10.7% | 9 |
| South Asian | 8.85% | 11 |
| Remaining individualsnot grpmax-eligible | 8.71% | 11 |
| European (non-Finnish) | 7.35% | 14 |
| Finnishnot grpmax-eligible | 6.59% | 15 |
| Admixed American | 6.42% | 16 |
| East Asian | 0.129% | 774 |
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.Cys147=
- Coding
- c.441C>T
- MANE Select
- NM_001734
- dbSNP
- rs7965055
- Type
- single nucleotide variant
- Location
- chr12:7064316 (GRCh38)
- Gene constraint
- LOEUF 0.783 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.02 · 14 PDB
- Residue 147
- a disulfide bond; the egf-like; calcium-binding domain; a β-strand
Similar variants
- 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
- C1S p.Ala649Thr 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-cys147 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown