Is CLN3 p.Ser336fs (c.1006dup) pathogenic?

CLN3 p.Ser336fs (c.1006dup) is classified Likely pathogenic in CLN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). Associated with neuronal ceroid lipofuscinosis 3.

What condition is associated with CLN3 p.Ser336fs (c.1006dup)?

CLN3 p.Ser336fs (c.1006dup) is associated with neuronal ceroid lipofuscinosis 3 (ClinVar).

How is CLN3 disease inherited?

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

CLN3 p.Ser336fs

c.1006dup · VCV4849412

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neuronal ceroid lipofuscinosis 3

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 14 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1

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

Variant & gene context

Gene: CLN3
Protein: p.Ser336fs
Coding: c.1006dup
MANE Select: NM_001042432
Type: Duplication
Location: chr16:28482154 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.81

Full CLN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN3 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CLN3 p.Ala191fs Pathogenic ★★ same condition
CLN3 p.Arg127fs Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Ser208fs Pathogenic ★★ same condition
CLN3 p.Val374fs Pathogenic/Likely pathogenic ★★ same condition
CLN3 c.461dup Likely pathogenic ★ same condition
CLN3 p.Cys353fs Likely pathogenic ★ same condition
CLN3 p.Leu122fs Likely pathogenic ★ same condition
CLN3 p.Thr80fs 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/cln3-p-ser336fs (accessed [today's date]).

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