Is CIC p.His1021fs (c.3059dup) pathogenic?

CIC p.His1021fs (c.3059dup) is classified Pathogenic in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). Absent from gnomAD; Associated with autosomal dominant non-syndromic intellectual disability.

What condition is associated with CIC p.His1021fs (c.3059dup)?

CIC p.His1021fs (c.3059dup) is associated with autosomal dominant non-syndromic intellectual disability (ClinVar).

How common is CIC p.His1021fs (c.3059dup) in the general population?

CIC p.His1021fs (c.3059dup) is absent from gnomAD (gnomAD).

CIC p.His1021fs

c.3059dup · rs2513811168 · VCV1708217

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal dominant non-syndromic intellectual disability

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 2.4	GERP 1.2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.His1021fs
Coding: c.3059dup
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs2513811168
Type: Duplication
Location: chr19:42287115 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Disease context

autosomal dominant non-syndromic intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
CIC p.Gly1628fs 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-his1021fs (accessed [today's date]).

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