Is CIC p.Arg688fs (c.2062dup) pathogenic?

CIC p.Arg688fs (c.2062dup) is classified Pathogenic in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal dominant 45.

What condition is associated with CIC p.Arg688fs (c.2062dup)?

CIC p.Arg688fs (c.2062dup) is associated with intellectual developmental disorder, autosomal dominant 45 (ClinVar).

How common is CIC p.Arg688fs (c.2062dup) in the general population?

CIC p.Arg688fs (c.2062dup) is absent from gnomAD v4.1 (gnomAD).

CIC p.Arg688fs

c.2062dup · VCV4891278

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 398,620)

Conditions

intellectual developmental disorder, autosomal dominant 45

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 7.4	GERP 1.2, phastCons 1

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 398,620). 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.Arg688fs
Coding: c.2062dup
MANE Select: NM_005984 · reported on NM_001386298
Type: Duplication
Location: chr19:42273839 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Disease context

intellectual developmental disorder, autosomal dominant 45 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIC p.Pro2507fs Uncertain significance ★★ same condition
CIC p.Cys397fs Likely pathogenic ★ same condition
CIC p.Gly1425fs Pathogenic ★ same condition
CIC p.Pro368fs Pathogenic ★ same condition
CIC p.Ser2026fs Pathogenic ★ same condition
CIC p.Trp343fs Likely pathogenic ★ same condition
CIC p.Arg688Gln Uncertain significance ★ same residue
CIC p.Pro2503fs Uncertain significance ★ same condition

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-arg688fs (accessed [today's date]).

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