Is CTSF p.Trp296Cys (c.888G>T) pathogenic?

CTSF p.Trp296Cys (c.888G>T) is classified Uncertain significance in CTSF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-12). AlphaMissense: likely pathogenic (0.996); Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis 13.

What condition is associated with CTSF p.Trp296Cys (c.888G>T)?

CTSF p.Trp296Cys (c.888G>T) is associated with neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Trp296Cys (c.888G>T) in the general population?

CTSF p.Trp296Cys (c.888G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSF p.Trp296Cys (c.888G>T)?

AlphaMissense predicts likely pathogenic (score 0.996) — an in-silico prediction, not a clinical call.

CTSF p.Trp296Cys

c.888G>T · rs746013208 · VCV2097195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis 13

Computational evidence

Protein change
AlphaMissense	0.996	likely pathogenic · top 1% in CTSF
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -17.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 4,550 bp · p 0.69 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTSF
Protein: p.Trp296Cys
Coding: c.888G>T
MANE Select: NM_003793
dbSNP: rs746013208
Type: single nucleotide variant
Location: chr11:66565907 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB
Residue 296: a disulfide bond; an α-helix

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.Trp296Ter Likely pathogenic ★ same residue
CTSF c.1045+1G>T Likely pathogenic ★★ same condition
CTSF p.Ala22Ser Uncertain significance ★★ ⚠ same condition
CTSF p.Arg196Gln Uncertain significance ★★ ⚠ same condition
CTSF p.Arg205Trp Uncertain significance ★★ ⚠ same condition
CTSF p.Arg413Cys Uncertain significance ★★ ⚠ same condition
CTSF p.Gly415Arg Uncertain significance ★★ ⚠ same condition
CTSF p.Gly439Ser 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-trp296cys (accessed [today's date]).

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