C2 p.Ser456fs
c.1366_1367del · VCV4800554
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 11 of 18 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 4.5 | GERP 0.79, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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
- C2
- Protein
- p.Ser456fs
- Coding
- c.1366_1367del
- MANE Select
- NM_000063
- Type
- Microsatellite
- Location
- chr6:31943228 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.61 · 14 PDB
Similar variants
- C2 p.Ser456Ala Uncertain significance ★ ⚠ same residue
- C2 p.Lys610fs Likely pathogenic ★★ same type
- C2 c.1811-5TA[3] Likely benign ★★ same type
- C2 p.Leu79fs Pathogenic ★ same type
- C2 p.Ser266fs Pathogenic ★ same type
- C2 p.Tyr210fs Pathogenic ★ same type
- C2 c.1219+22_1219+24del Likely benign ★ same type
- C2 c.257-12CT[3] Likely benign ★ 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/c2-p-ser456fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown