Is PPT1 p.Val92= (c.276A>G) pathogenic?

PPT1 p.Val92= (c.276A>G) is classified Likely benign in PPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-10). Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis 1.

What condition is associated with PPT1 p.Val92= (c.276A>G)?

PPT1 p.Val92= (c.276A>G) is associated with neuronal ceroid lipofuscinosis 1 (ClinVar).

How common is PPT1 p.Val92= (c.276A>G) in the general population?

PPT1 p.Val92= (c.276A>G) is absent from gnomAD v4.1 (gnomAD).

How is CLN1 disease inherited?

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

PPT1 p.Val92=

c.276A>G · rs1379772634 · VCV2694774

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neuronal ceroid lipofuscinosis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -4.6
Overall
CADD	1.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPT1
Protein: p.Val92=
Coding: c.276A>G
MANE Select: NM_000310
dbSNP: rs1379772634
Type: single nucleotide variant
Location: chr1:40092131 (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 92: 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 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-val92 (accessed [today's date]).

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