Is CLN8 p.Ala80fs (c.237del) pathogenic?

CLN8 p.Ala80fs (c.237del) is classified Pathogenic in CLN8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN8 p.Ala80fs (c.237del)?

CLN8 p.Ala80fs (c.237del) is associated with neuronal ceroid lipofuscinosis (ClinVar).

CLN8 p.Ala80fs

c.237del · VCV3640321

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neuronal ceroid lipofuscinosis

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 -0.75	GERP -4

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

Variant & gene context

Gene: CLN8
Protein: p.Ala80fs
Coding: c.237del
MANE Select: NM_018941
Type: Deletion
Location: chr8:1771290 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.47 · 3 PDB
Residue 80: the tlc domain

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

Disease context

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

Similar variants

CLN8 p.Ala80Thr Uncertain significance ★★ ⚠ same residue
CLN8 p.Arg54fs Pathogenic ★ same condition
CLN8 p.Asp15fs Likely pathogenic ★ same condition
CLN8 p.Asp88fs Pathogenic ★ same condition
CLN8 p.Glu186fs Pathogenic ★ same condition
CLN8 p.Gly183fs Pathogenic ★ same condition
CLN8 p.His106fs Pathogenic ★ same condition
CLN8 p.Ile23_Ser25del 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-ala80fs (accessed [today's date]).

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