Is PPT1 p.Phe147fs (c.440_441del) pathogenic?

PPT1 p.Phe147fs (c.440441del) is classified Pathogenic in PPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-07). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis 1.

What condition is associated with PPT1 p.Phe147fs (c.440_441del)?

PPT1 p.Phe147fs (c.440_441del) is associated with neuronal ceroid lipofuscinosis 1 (ClinVar).

How common is PPT1 p.Phe147fs (c.440_441del) in the general population?

PPT1 p.Phe147fs (c.440_441del) is absent from gnomAD (gnomAD).

How is CLN1 disease inherited?

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

PPT1 p.Phe147fs

c.440_441del · rs2523675796 · VCV2110798

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, 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.Phe147fs
Coding: c.440_441del
MANE Select: NM_000310
dbSNP: rs2523675796
Type: Deletion
Location: chr1:40089505 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.05 · 1 PDB

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.Phe147Ser Uncertain significance ★★ ⚠ same residue
PPT1 p.Phe147= 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
PPT1 p.Met133fs 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-phe147fs (accessed [today's date]).

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