Is CTSF p.Pro126fs (c.375_382del) pathogenic?

CTSF p.Pro126fs (c.375382del) is classified Pathogenic in CTSF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). Associated with neuronal ceroid lipofuscinosis 13.

What condition is associated with CTSF p.Pro126fs (c.375_382del)?

CTSF p.Pro126fs (c.375_382del) is associated with neuronal ceroid lipofuscinosis 13 (ClinVar).

CTSF p.Pro126fs

c.375_382del · VCV4724736

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neuronal ceroid lipofuscinosis 13

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 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP 0.14, phastCons 1

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

Variant & gene context

Gene: CTSF
Protein: p.Pro126fs
Coding: c.375_382del
MANE Select: NM_003793
Type: Deletion
Location: chr11:66567593 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB

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

Disease context

neuronal ceroid lipofuscinosis 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN13 disease (Orphanet):

Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

CTSF c.1380+19del Likely benign ★★ same condition
CTSF c.530_531+11del Likely pathogenic ★ same condition
CTSF p.Ala282fs Pathogenic ★ same condition
CTSF p.Gly439fs Likely pathogenic ★ same condition
CTSF p.Met291fs Pathogenic ★ same condition
CTSF p.Val110fs Pathogenic ★ same condition
CTSF p.Ala391fs Conflicting classifications of pathogenicity ★ same condition
CTSF p.Ala82_Glu85del 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/ctsf-p-pro126fs (accessed [today's date]).

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