Is USP8 p.Leu795= (c.2383C>T) pathogenic?

USP8 p.Leu795= (c.2383C>T) is classified Likely benign in USP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-27). Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia.

What condition is associated with USP8 p.Leu795= (c.2383C>T)?

USP8 p.Leu795= (c.2383C>T) is associated with hereditary spastic paraplegia (ClinVar).

How common is USP8 p.Leu795= (c.2383C>T) in the general population?

USP8 p.Leu795= (c.2383C>T) is absent from gnomAD v4.1 (gnomAD).

USP8 p.Leu795=

c.2383C>T · rs1595985288 · VCV795843

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary spastic paraplegia

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 5.9	GERP 2.2, phastCons 1
Overall
CADD	13.03	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: USP8
Protein: p.Leu795=
Coding: c.2383C>T
MANE Select: NM_005154
dbSNP: rs1595985288
Type: single nucleotide variant
Location: chr15:50492849 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.98 · 9 PDB
Residue 795: the usp domain; an α-helix

Full USP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USP8 p.Arg133Trp Uncertain significance ★★ ⚠ same condition
USP8 p.Phe875Ser Uncertain significance ★★ ⚠ same condition
USP8 p.Pro703His Uncertain significance ★★ ⚠ same condition
USP8 c.104+16C>T Benign ★★ same condition
USP8 c.250-8A>C Benign ★★ same condition
USP8 p.Ala348Thr Benign ★★ same condition
USP8 p.Arg483Gln Benign ★★ same condition
USP8 p.Arg763Trp Benign ★★ ⚠ 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/usp8-p-leu795 (accessed [today's date]).

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