Is PPT1 p.Arg151Ter (c.451C>T) pathogenic?

PPT1 p.Arg151Ter (c.451C>T) is classified Pathogenic/Likely pathogenic in PPT1 (ClinVar, Multiple submitters, 38 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0596%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with PPT1 p.Arg151Ter (c.451C>T)?

PPT1 p.Arg151Ter (c.451C>T) is associated with neuronal ceroid lipofuscinosis, retinal disorder, neuronal ceroid lipofuscinosis 1 (ClinVar).

How common is PPT1 p.Arg151Ter (c.451C>T) in the general population?

PPT1 p.Arg151Ter (c.451C>T) is ultra-rare (popmax 0.0596%, nfe) (gnomAD).

PPT1 p.Arg151Ter

c.451C>T · rs137852700 · VCV8904

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 38 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0596%, nfe)

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 9
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.29	loss · gain 0.02 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 6.6	GERP 2.1, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0596% European (non-Finnish) · 703/1,179,960 alleles

Filtering AF 0.0559% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0544%

Overall 0.0454% 732/1,613,878 alleles · ultra-rare exomes 678/1,461,812 · genomes 54/152,066 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0596%	1,678
Remaining individualsnot grpmax-eligible	0.0288%	3,471
African / African-American	0.0107%	9,360
Admixed American	0.005%	19,998

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.Arg151Ter
Coding: c.451C>T
MANE Select: NM_000310
dbSNP: rs137852700
Type: single nucleotide variant
Location: chr1:40089495 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinal disorder neuronal ceroid lipofuscinosis 1

Similar variants

PPT1 p.Arg151Gln Uncertain significance ★★ ⚠ same residue
PPT1 p.Arg151Gly Uncertain significance ★ ⚠ same residue
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

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-arg151ter (accessed [today's date]).

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