Is CTSD p.Val174fs (c.519dup) pathogenic?

CTSD p.Val174fs (c.519dup) is classified Pathogenic in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Val174fs (c.519dup)?

CTSD p.Val174fs (c.519dup) is associated with neuronal ceroid lipofuscinosis (ClinVar).

CTSD p.Val174fs

c.519dup · VCV3664390

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -0.85, phastCons 0.89

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

Variant & gene context

Gene: CTSD
Protein: p.Val174fs
Coding: c.519dup
MANE Select: NM_001909
Type: Duplication
Location: chr11:1757508 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 174: a β-strand; the peptidase a1 domain

Full CTSD 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

CTSD p.Leu11fs Pathogenic ★★ same condition
CTSD c.675_704+1dup Likely pathogenic ★ same condition
CTSD p.Ala314fs Pathogenic ★ same condition
CTSD p.Glu352fs Pathogenic ★ same condition
CTSD p.Lys253fs Pathogenic ★ same condition
CTSD p.Val156fs Pathogenic ★ same condition
CTSD c.972+4_972+5dup Uncertain significance ★ same condition
CTSD p.Glu278_Val279insGlu 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/ctsd-p-val174fs (accessed [today's date]).

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