Is CTSD p.Pro381fs (c.1142del) pathogenic?

CTSD p.Pro381fs (c.1142del) is classified Uncertain significance in CTSD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-25). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Pro381fs (c.1142del)?

CTSD p.Pro381fs (c.1142del) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Pro381fs (c.1142del) in the general population?

CTSD p.Pro381fs (c.1142del) is absent from gnomAD (gnomAD).

CTSD p.Pro381fs

c.1142del · rs2493816019 · VCV2130707

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -20

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTSD
Protein: p.Pro381fs
Coding: c.1142del
MANE Select: NM_001909
dbSNP: rs2493816019
Type: Deletion
Location: chr11:1753600 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 381: 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.Gln90fs Pathogenic/Likely pathogenic ★★ same condition
CTSD p.Val318fs Pathogenic/Likely pathogenic ★★ same condition
CTSD p.Val52fs Pathogenic/Likely pathogenic ★★ same condition
CTSD c.828-14_828-13del Benign/Likely benign ★★ same condition
CTSD c.824_827+30del Likely pathogenic ★ same condition
CTSD p.Ala18fs Pathogenic ★ same condition
CTSD p.Ala317fs Pathogenic ★ same condition
CTSD p.Asn209fs 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-pro381fs (accessed [today's date]).

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