Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively-inherited neurodegenerative disorder caused by intronic biallelic, non-reference CCCTT/AAGGG repeat expansions within RFC1. To investigate how these repeats cause disease, we generated patient induced pluripotent stem cell (iPSC)-derived neurons (iNeurons). CCCTT/AAGGG repeat expansions do not alter neuronal RFC1 splicing, expression, or DNA repair pathway function. In reporter assays, AAGGG repeats are translated into pentapeptide repeat proteins and we observe these peptides in patient brains. CANVAS iNeurons exhibit defects in neuronal development and diminished synaptic connectivity that is rescued by CRISPR deletion of a single expanded AAGGG allele. These deficits were neither replicated by RFC1 knockdown in control iNeurons, nor rescued by RFC1 reprovision in CANVAS iNeurons. These findings support a repeat-dependent but RFC1 protein-independent cause of neuronal dysfunction in CANVAS, with implications for therapeutic development in this currently untreatable condition.