Is CLN5 p.Ser42fs (c.114_124dup) pathogenic?

CLN5 p.Ser42fs (c.114124dup) is classified Likely pathogenic in CLN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). Very rare (popmax 8.49e-05%, nfe); Associated with neuronal ceroid lipofuscinosis 5.

What condition is associated with CLN5 p.Ser42fs (c.114_124dup)?

CLN5 p.Ser42fs (c.114_124dup) is associated with neuronal ceroid lipofuscinosis 5 (ClinVar).

How common is CLN5 p.Ser42fs (c.114_124dup) in the general population?

CLN5 p.Ser42fs (c.114_124dup) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

CLN5 p.Ser42fs

c.114_124dup · rs2501124958 · VCV2680835

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

neuronal ceroid lipofuscinosis 5

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 1 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 1.2, phastCons 0.18

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,740 alleles

Overall 6.9e-05% 1/1,450,276 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: CLN5
Protein: p.Ser42fs
Coding: c.114_124dup
MANE Select: NM_006493
dbSNP: rs2501124958
Type: Duplication
Location: chr13:76992207 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 1 PDB

Full CLN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN5 disease (Orphanet):

Onset: Infancy

Similar variants

CLN5 p.Asn240Ter Pathogenic/Likely pathogenic ★★ same condition
CLN5 p.Asp172fs Pathogenic/Likely pathogenic ★★ same condition
CLN5 p.His148fs Pathogenic/Likely pathogenic ★★ same condition
CLN5 p.Ser49fs Pathogenic/Likely pathogenic ★★ same condition
CLN5 p.Trp175fs Pathogenic ★★ same condition
CLN5 p.Met116fs Likely pathogenic ★ same condition
CLN5 p.Tyr343fs Likely pathogenic ★ same condition
CLN5 p.Thr127fs 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/cln5-p-ser42fs (accessed [today's date]).

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