Is CTSF p.Lys374fs (c.1119dup) pathogenic?

CTSF p.Lys374fs (c.1119dup) is classified Pathogenic in CTSF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). Very rare (popmax 8.52e-05%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSF p.Lys374fs (c.1119dup)?

CTSF p.Lys374fs (c.1119dup) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSF p.Lys374fs (c.1119dup) in the general population?

CTSF p.Lys374fs (c.1119dup) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

CTSF p.Lys374fs

c.1119dup · rs2495273817 · VCV2691546

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

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 9 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 2.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,294 alleles

Overall 6.88e-05% 1/1,452,748 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: CTSF
Protein: p.Lys374fs
Coding: c.1119dup
MANE Select: NM_003793
dbSNP: rs2495273817
Type: Duplication
Location: chr11:66564932 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTSF p.Lys331fs Pathogenic/Likely pathogenic ★★ same condition
CTSF p.Ala56fs Likely pathogenic ★ same condition
CTSF p.Arg44fs Likely pathogenic ★ same condition
CTSF p.Cys89fs Likely pathogenic ★ same condition
CTSF p.Ser36fs Likely pathogenic ★ same condition
CTSF p.Thr197_Tyr198insTer Pathogenic ★ same condition
CTSF c.1046-2A>C Conflicting classifications of pathogenicity ★ same condition
CTSF p.Ser480Leu Conflicting classifications of pathogenicity ★ ⚠ 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-lys374fs (accessed [today's date]).

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