PGPEP1L

Chr 15

pyroglutamyl-peptidase I like

The protein is predicted to function as a pyroglutamyl-peptidase involved in proteolysis within the cytosol. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene shows very low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

ResearchSummary from RefSeq
LOEUF 1.95
Clinical SummaryPGPEP1L
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
85 unique Pathogenic / Likely Pathogenic· 78 VUS of 169 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.95LOEUF
pLI 0.000
Z-score -1.54
OE 1.68 (0.961.95)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.09Z-score
OE missense 1.28 (1.121.46)
154 obs / 120.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.68 (0.961.95)
00.351.4
Missense OE1.28 (1.121.46)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 10 / 5.9Missense obs/exp: 154 / 120.2Syn Z: -1.65

ClinVar Variant Classifications

169 submitted variants in ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic8
VUS78
Likely Benign5
77
Pathogenic
8
Likely Pathogenic
78
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
77
0
77
Likely Pathogenic
0
0
8
0
8
VUS
0
53
25
0
78
Likely Benign
0
4
0
1
5
Benign
0
0
0
0
0
Total0571101168

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PGPEP1L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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