Is CLN8 p.Ala30fs (c.88del) pathogenic?

CLN8 p.Ala30fs (c.88del) is classified Pathogenic/Likely pathogenic in CLN8 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2001-01-01). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis 8.

What condition is associated with CLN8 p.Ala30fs (c.88del)?

CLN8 p.Ala30fs (c.88del) is associated with neuronal ceroid lipofuscinosis 8 (ClinVar).

How common is CLN8 p.Ala30fs (c.88del) in the general population?

CLN8 p.Ala30fs (c.88del) is absent from gnomAD (gnomAD).

How is CLN8 disease inherited?

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

CLN8 p.Ala30fs

c.88del · rs386834139 · VCV56720

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

Not reported

no gnomAD frequency available for this variant

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 -12	GERP -4

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: CLN8
Protein: p.Ala30fs
Coding: c.88del
MANE Select: NM_018941
dbSNP: rs386834139
Type: Deletion
Location: chr8:1771142 (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 30: a UniProt-annotated variant site (in cln8)

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.Ala30Ser Uncertain significance ★ ⚠ same residue
CLN8 p.Ala30Pro Pathogenic same residue
CLN8 p.Ala30Thr Uncertain significance ★★ ⚠ 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.Ala30= Likely benign ★ same residue

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-ala30fs (accessed [today's date]).

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