Is TPP1 p.Val204fs (c.609dup) pathogenic?

TPP1 p.Val204fs (c.609dup) is classified Pathogenic in TPP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-03). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis 2.

What condition is associated with TPP1 p.Val204fs (c.609dup)?

TPP1 p.Val204fs (c.609dup) is associated with neuronal ceroid lipofuscinosis 2 (ClinVar).

How common is TPP1 p.Val204fs (c.609dup) in the general population?

TPP1 p.Val204fs (c.609dup) is absent from gnomAD (gnomAD).

How is CLN2 disease inherited?

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

TPP1 p.Val204fs

c.609dup · rs1057516366 · VCV370272

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neuronal ceroid lipofuscinosis 2

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 6 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.3, phastCons 1

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: TPP1
Protein: p.Val204fs
Coding: c.609dup
MANE Select: NM_000391
dbSNP: rs1057516366
Type: Duplication
Location: chr11:6617052 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.70 · 2 PDB
Residue 204: the peptidase s53 domain; an α-helix

Full TPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN2 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

TPP1 p.Leu120fs Pathogenic ★★ same condition
TPP1 p.Leu500fs Pathogenic/Likely pathogenic ★★ same condition
TPP1 p.Ser113fs Pathogenic/Likely pathogenic ★★ same condition
TPP1 c.381-10dup Benign ★★ same condition
TPP1 p.Arg268fs Pathogenic ★ same condition
TPP1 p.Glu532fs Pathogenic ★ same condition
TPP1 p.Ile484fs Pathogenic ★ same condition
TPP1 p.Leu80fs 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/tpp1-p-val204fs (accessed [today's date]).

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