Is CLN8 p.Ile23fs (c.66del) pathogenic?

CLN8 p.Ile23fs (c.66del) is classified Pathogenic/Likely pathogenic in CLN8 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2006-05-01). Very rare (popmax 8.47e-05%, nfe); Associated with neuronal ceroid lipofuscinosis 8.

What condition is associated with CLN8 p.Ile23fs (c.66del)?

CLN8 p.Ile23fs (c.66del) is associated with neuronal ceroid lipofuscinosis 8 (ClinVar).

How common is CLN8 p.Ile23fs (c.66del) in the general population?

CLN8 p.Ile23fs (c.66del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is CLN8 disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CLN8 p.Ile23fs

c.66del · rs34238807 · VCV56718

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

neuronal ceroid lipofuscinosis 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP 2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 6.84e-05% 1/1,461,892 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CLN8
Protein: p.Ile23fs
Coding: c.66del
MANE Select: NM_018941
dbSNP: rs34238807
Type: Deletion
Location: chr8:1771116 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.47 · 3 PDB

Full CLN8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN8 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CLN8 p.Ile23_Ser25del Pathogenic ★ same residue
CLN8 p.Asp88fs Pathogenic ★ same condition
CLN8 p.Met1* Pathogenic ★ same condition
CLN8 p.Gly276fs Conflicting classifications of pathogenicity ★ same condition
CLN8 p.Trp213fs Conflicting classifications of pathogenicity ★ same condition
CLN8 p.Ala30fs Pathogenic/Likely pathogenic same condition
CLN8 p.Asp17fs Likely pathogenic same condition
CLN8 p.His199fs Likely pathogenic 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/cln8-p-ile23fs (accessed [today's date]).

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