CIC p.Pro1418fs
c.4253del · VCV3368069
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 10 | GERP 0.42, 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
- CIC
- Protein
- p.Pro1418fs
- Coding
- c.4253del
- MANE Select
- NM_005984 · reported on NM_001386298
- Type
- Deletion
- Location
- chr19:42290289 (GRCh38)
- Structure
- AlphaFold pLDDT 75.09
Similar variants
- CIC p.Pro788fs Pathogenic/Likely pathogenic ★★ same type
- SLC25A1 p.Arg173fs Pathogenic/Likely pathogenic ★★ same type
- CIC c.2795-3881_5255del Pathogenic ★ same type
- CIC p.Ala1339fs Likely pathogenic ★ same type
- CIC p.Ala1694fs Likely pathogenic ★ same type
- CIC p.Ala1809fs Likely pathogenic ★ same type
- CIC p.Ala2056fs Pathogenic ★ same type
- CIC p.Arg1110fs Likely 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/cic-p-pro1418fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown