Is CLN8 p.Val38fs (c.109_112dup) pathogenic?

CLN8 p.Val38fs (c.109112dup) is classified Pathogenic in CLN8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-13). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN8 p.Val38fs (c.109_112dup)?

CLN8 p.Val38fs (c.109_112dup) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN8 p.Val38fs (c.109_112dup) in the general population?

CLN8 p.Val38fs (c.109_112dup) is absent from gnomAD (gnomAD).

CLN8 p.Val38fs

c.109_112dup · rs2486437938 · VCV2019654

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 5.9	GERP 0.94, phastCons 1

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.Val38fs
Coding: c.109_112dup
MANE Select: NM_018941
dbSNP: rs2486437938
Type: Duplication
Location: chr8:1771161 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLN8 p.Val38Ile Uncertain significance ★★ ⚠ same residue
CLN8 p.Val38Phe Uncertain significance ★★ same residue
CLN8 p.Val38= Likely benign ★ same residue
CLN8 p.Met200fs Pathogenic/Likely pathogenic ★★ same condition
CLN8 c.-125_-124+19dup Uncertain significance ★★ same condition
CLN8 p.Ala160fs Pathogenic ★ same condition
CLN8 p.Asp94fs Pathogenic ★ same condition
CLN8 p.Pro268fs 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/cln8-p-val38fs (accessed [today's date]).

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