Is CIC p.Lys1808fs (c.5421dup) pathogenic?

CIC p.Lys1808fs (c.5421dup) is classified Pathogenic in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-08). Absent from gnomAD v4.1.

How common is CIC p.Lys1808fs (c.5421dup) in the general population?

CIC p.Lys1808fs (c.5421dup) is absent from gnomAD v4.1 (gnomAD).

CIC p.Lys1808fs

c.5421dup · rs1555770200 · VCV422592

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,968)

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 -2.3	GERP -1.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,968). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CIC
Protein: p.Lys1808fs
Coding: c.5421dup
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs1555770200
Type: Duplication
Location: chr19:42291456 (GRCh38)
Structure: AlphaFold pLDDT 75.09

Full CIC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIC p.Lys1808Glu Uncertain significance ★★ ⚠ same residue
CIC p.Pro2483_Leu2484insGlnAlaAlaProPro Uncertain significance ★★ same type
CIC p.Pro2507fs Uncertain significance ★★ same type
CIC p.Ala1975fs Likely pathogenic ★ same type
CIC p.Arg688fs Pathogenic ★ same type
CIC p.Asp2349fs Pathogenic ★ same type
CIC p.Cys397fs Likely pathogenic ★ same type
CIC p.Gly1425fs 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-lys1808fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown