Is CTSD p.Gly343fs (c.1028del) pathogenic?

CTSD p.Gly343fs (c.1028del) is classified Pathogenic in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-11). Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Gly343fs (c.1028del)?

CTSD p.Gly343fs (c.1028del) is associated with neuronal ceroid lipofuscinosis (ClinVar).

CTSD p.Gly343fs

c.1028del · VCV4706655

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (8 of 9, 43 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.8

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

Variant & gene context

Gene: CTSD
Protein: p.Gly343fs
Coding: c.1028del
MANE Select: NM_001909
Type: Deletion
Location: chr11:1753846 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 343: a disulfide bond; 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.Gly343Glu Uncertain significance ★★ ⚠ same residue
CTSD p.Gly343= Likely benign ★ same residue
CTSD p.Gln90fs Pathogenic/Likely pathogenic ★★ same condition
CTSD p.Val318fs Pathogenic/Likely pathogenic ★★ same condition
CTSD p.Val52fs Pathogenic/Likely pathogenic ★★ same condition
CTSD p.Pro381fs Uncertain significance ★★ same condition
CTSD c.828-14_828-13del Benign/Likely benign ★★ same condition
CTSD c.824_827+30del Likely 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/ctsd-p-gly343fs (accessed [today's date]).

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