Is PPT1 p.Phe85del (c.249CTT[2]) pathogenic?

PPT1 p.Phe85del (c.249CTT[2]) is classified Likely pathogenic in PPT1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-02-23). Very rare (popmax 0.00153%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with PPT1 p.Phe85del (c.249CTT[2])?

PPT1 p.Phe85del (c.249CTT[2]) is associated with neuronal ceroid lipofuscinosis, neuronal ceroid lipofuscinosis 1 (ClinVar).

How common is PPT1 p.Phe85del (c.249CTT[2]) in the general population?

PPT1 p.Phe85del (c.249CTT[2]) is very rare (popmax 0.00153%, nfe) (gnomAD).

PPT1 p.Phe85del

c.249CTT[2] · rs386833637 · VCV56185

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Conditions

neuronal ceroid lipofuscinosis

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 2.6	GERP 1.4, phastCons 1
Overall
CADD	19.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,179,998 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,613,990 alleles · very rare exomes 16/1,461,824 · genomes 2/152,166 · joint denominator

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.Phe85del
Coding: c.249CTT[2]
MANE Select: NM_000310
dbSNP: rs386833637
Type: Microsatellite
Location: chr1:40092150 (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 85: an α-helix

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

Disease context

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

Also linked: neuronal ceroid lipofuscinosis 1

Similar variants

PPT1 p.Phe85= Likely benign ★ same residue
PPT1 p.Cys160_Asp161delinsTer Pathogenic ★ same condition
PPT1 p.Gln116fs Pathogenic ★ same condition
PPT1 c.124+2TGAG[2] Likely benign ★ same condition
PPT1 c.799-22_799-19del Likely benign ★ same condition
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

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-phe85del (accessed [today's date]).

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