C1S p.Val580fs
c.1737del · VCV4773897
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP -0.47, phastCons 0.97 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- C1S
- Protein
- p.Val580fs
- Coding
- c.1737del
- MANE Select
- NM_001734
- Type
- Deletion
- Location
- chr12:7070321 (GRCh38)
- Gene constraint
- LOEUF 0.783 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.02 · 14 PDB
- Residue 580
- the peptidase s1 domain
Similar variants
- C1S p.Ser115fs Pathogenic ★★ same type
- C1S c.518-13_518-6del Benign/Likely benign ★★ same type
- C1S c.6-10_6-9del Likely benign ★★ same type
- C1S p.Arg481fs Pathogenic ★ same type
- C1S p.Asn233fs Pathogenic ★ same type
- C1S p.Asn27fs Pathogenic ★ same type
- C1S p.Asn344fs Pathogenic ★ same type
- C1S p.Asp315_Val316delinsGlu Pathogenic ★ 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-val580fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown