Is PPT1 p.Ile72= (c.216T>C) pathogenic?

PPT1 p.Ile72= (c.216T>C) is classified Likely benign in PPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). Very rare (popmax 0.000594%, nfe); Associated with neuronal ceroid lipofuscinosis 1.

What condition is associated with PPT1 p.Ile72= (c.216T>C)?

PPT1 p.Ile72= (c.216T>C) is associated with neuronal ceroid lipofuscinosis 1 (ClinVar).

How common is PPT1 p.Ile72= (c.216T>C) in the general population?

PPT1 p.Ile72= (c.216T>C) is very rare (popmax 0.000594%, nfe) (gnomAD).

How is CLN1 disease inherited?

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

PPT1 p.Ile72=

c.216T>C · rs998610907 · VCV2877701

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000594%, nfe)

Conditions

neuronal ceroid lipofuscinosis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP 0.023, phastCons 1
Overall
CADD	9.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000594% European (non-Finnish) · 7/1,177,804 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00048% 7/1,459,380 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PPT1
Protein: p.Ile72=
Coding: c.216T>C
MANE Select: NM_000310
dbSNP: rs998610907
Type: single nucleotide variant
Location: chr1:40092416 (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 c.234+1G>A Pathogenic ★★ same condition
PPT1 c.362+1G>A Likely pathogenic ★★ same condition
PPT1 c.433+1G>A Pathogenic ★★ same condition
PPT1 c.627+1G>T Likely pathogenic ★★ same condition
PPT1 c.628-1G>T Pathogenic ★★ same condition
PPT1 c.628-2A>G Pathogenic/Likely pathogenic ★★ same condition
PPT1 c.727-2A>T Pathogenic/Likely pathogenic ★★ same condition
PPT1 c.798+1G>T 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-ile72 (accessed [today's date]).

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