Is PPT1 p.Ser241fs (c.721del) pathogenic?

PPT1 p.Ser241fs (c.721del) is classified Pathogenic in PPT1 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-01-22). No gnomAD frequency available for this variant; Associated with neuronal ceroid lipofuscinosis 1.

What condition is associated with PPT1 p.Ser241fs (c.721del)?

PPT1 p.Ser241fs (c.721del) is associated with neuronal ceroid lipofuscinosis 1 (ClinVar).

How common is PPT1 p.Ser241fs (c.721del) in the general population?

PPT1 p.Ser241fs (c.721del) is no gnomAD frequency available for this variant (gnomAD).

How is CLN1 disease inherited?

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

PPT1 p.Ser241fs

c.721del · rs1553166499 · VCV557311

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 1

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 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 2.3, 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: PPT1
Protein: p.Ser241fs
Coding: c.721del
MANE Select: NM_000310
dbSNP: rs1553166499
Type: Deletion
Location: chr1:40078565 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.05 · 1 PDB
Residue 241: an α-helix

Full PPT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN1 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

PPT1 p.Ser241Ter Pathogenic ★ same residue
PPT1 p.Ser241Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PPT1 p.Ser241= Likely benign ★ same residue
PPT1 c.799del Likely pathogenic ★★ same condition
PPT1 p.Cys152fs Pathogenic/Likely pathogenic ★★ same condition
PPT1 p.Glu59fs Pathogenic ★★ same condition
PPT1 p.Gly270_Leu271insTer Pathogenic/Likely pathogenic ★★ same condition
PPT1 p.Leu10fs Pathogenic/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/ppt1-p-ser241fs (accessed [today's date]).

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