CIC p.Ile1408Leu
c.4222A>C · VCV4848438
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4629 | ambiguous |
|---|---|---|
| REVEL | 0.279 | benign-leaning |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 22.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I499L vs ClinVar I1408L) — verify the residue.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CIC
- Protein
- p.Ile1408Leu
- Coding
- c.4222A>C
- MANE Select
- NM_005984 · reported on NM_001386298
- Type
- single nucleotide variant
- Location
- chr19:42290263 (GRCh38)
- Structure
- AlphaFold pLDDT 75.09
Similar variants
- CIC p.Ile1408Ser Uncertain significance ★ ⚠ same residue
- CIC p.Ile1408Thr Uncertain significance ★ same residue
- CIC c.3179+1G>A Likely pathogenic ★★ same type
- CIC c.3179+1G>T Pathogenic ★★ same type
- CIC c.5903-2A>G Likely pathogenic ★★ same type
- CIC p.Asn1136Ser Likely pathogenic ★★ same type
- CIC p.Gln1134Ter Pathogenic ★★ same type
- CIC p.Gln1799Ter 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-ile1408leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown