Is CTSF p.Ser319fs (c.954del) pathogenic?

CTSF p.Ser319fs (c.954del) is classified Pathogenic in CTSF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-04-01). Very rare (popmax 0.00941%, nfe); Associated with neuronal ceroid lipofuscinosis 13.

What condition is associated with CTSF p.Ser319fs (c.954del)?

CTSF p.Ser319fs (c.954del) is associated with neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Ser319fs (c.954del) in the general population?

CTSF p.Ser319fs (c.954del) is very rare (popmax 0.00941%, nfe) (gnomAD).

CTSF p.Ser319fs

c.954del · rs753084727 · VCV60679

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00941%, nfe)

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 7 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00941% European (non-Finnish) · 111/1,180,014 alleles

Filtering AF 0.00791% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00744%

Overall 0.00706% 114/1,613,854 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00941%	10,631
African / African-American	0.00267%	37,470
Admixed American	0.00167%	59,996

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.Ser319fs
Coding: c.954del
MANE Select: NM_003793
dbSNP: rs753084727
Type: Deletion
Location: chr11:66565841 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB
Residue 319: a disulfide bond

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 p.Ser319Ala Uncertain significance ★ ⚠ same residue
CTSF p.Ser319Phe Uncertain significance ★ ⚠ same residue
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.Pro126fs 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/ctsf-p-ser319fs (accessed [today's date]).

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