Is CLN5 p.Phe295fs (c.882dup) pathogenic?

CLN5 p.Phe295fs (c.882dup) is classified Pathogenic in CLN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-05). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN5 p.Phe295fs (c.882dup)?

CLN5 p.Phe295fs (c.882dup) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN5 p.Phe295fs (c.882dup) in the general population?

CLN5 p.Phe295fs (c.882dup) is absent from gnomAD (gnomAD).

CLN5 p.Phe295fs

c.882dup · rs2501157103 · VCV2823779

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	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP -1.9, 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: CLN5
Protein: p.Phe295fs
Coding: c.882dup
MANE Select: NM_006493
dbSNP: rs2501157103
Type: Duplication
Location: chr13:77000770 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLN5 p.Phe295Leu Uncertain significance ★★ ⚠ same residue
CLN5 p.Asn240Ter 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 c.566-8dup Benign/Likely benign ★★ same condition
CLN5 p.Asn255fs Pathogenic ★ same condition
CLN5 p.Glu12fs 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-phe295fs (accessed [today's date]).

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