Is CTSD p.Tyr255Ter (c.764dup) pathogenic?

CTSD p.Tyr255Ter (c.764dup) is classified Pathogenic in CTSD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-06-01). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis 10.

What condition is associated with CTSD p.Tyr255Ter (c.764dup)?

CTSD p.Tyr255Ter (c.764dup) is associated with neuronal ceroid lipofuscinosis 10 (ClinVar).

How common is CTSD p.Tyr255Ter (c.764dup) in the general population?

CTSD p.Tyr255Ter (c.764dup) is absent from gnomAD (gnomAD).

How is CLN10 disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CTSD p.Tyr255Ter

c.764dup · rs786205105 · VCV17575

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neuronal ceroid lipofuscinosis 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.61	GERP 0.68, phastCons 0.073

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.Tyr255Ter
Coding: c.764dup
MANE Select: NM_001909
dbSNP: rs786205105
Type: Duplication
Location: chr11:1754968 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 255: 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 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN10 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Antenatal, Infancy

Similar variants

CTSD p.Leu11fs Pathogenic ★★ same condition
CTSD c.*210C>G Uncertain significance ★★ same condition
CTSD p.Ala239Val Uncertain significance ★★ ⚠ same condition
CTSD p.Arg411His Uncertain significance ★★ ⚠ same condition
CTSD p.Glu310Lys Uncertain significance ★★ ⚠ same condition
CTSD p.Gly316Arg Uncertain significance ★★ ⚠ same condition
CTSD p.Gly362Arg Uncertain significance ★★ ⚠ same condition
CTSD p.His273Tyr 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-tyr255ter (accessed [today's date]).

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