Is TPP1 c.90del pathogenic?

TPP1 c.90del is classified Pathogenic/Likely pathogenic in TPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-22). No gnomAD frequency available for this variant; Associated with neuronal ceroid lipofuscinosis 2.

What condition is associated with TPP1 c.90del?

TPP1 c.90del is associated with neuronal ceroid lipofuscinosis 2 (ClinVar).

How common is TPP1 c.90del in the general population?

TPP1 c.90del is no gnomAD frequency available for this variant (gnomAD).

How is CLN2 disease inherited?

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

TPP1 c.90del

rs2493802191 · VCV2089504

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP -3.5, phastCons 1
Non-coding constraint	Z 2.26	1 kb window · o/e 0.85 · regional · uncalibrated

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
Coding: c.90del
MANE Select: NM_000391
dbSNP: rs2493802191
Type: Deletion
Location: chr11:6618915 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.70 · 2 PDB

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 c.1363_1425+9del Pathogenic/Likely pathogenic ★★ same condition
TPP1 c.376_380+6del Pathogenic ★★ same condition
TPP1 p.Arg497fs Pathogenic/Likely pathogenic ★★ same condition
TPP1 p.Asn313fs Pathogenic ★★ same condition
TPP1 p.Gly501fs Pathogenic/Likely pathogenic ★★ same condition
TPP1 p.His491fs Pathogenic/Likely pathogenic ★★ same condition
TPP1 p.Leu49fs Pathogenic/Likely pathogenic ★★ same condition
TPP1 p.Leu515_Phe516insTer 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-c-90del (accessed [today's date]).

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