Is USP45 p.Asp293fs (c.878_881del) pathogenic?

USP45 p.Asp293fs (c.878881del) is classified Likely pathogenic in USP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). Associated with Leber congenital amaurosis 19.

What condition is associated with USP45 p.Asp293fs (c.878_881del)?

USP45 p.Asp293fs (c.878_881del) is associated with Leber congenital amaurosis 19 (ClinVar).

How is Leber congenital amaurosis inherited?

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

USP45 p.Asp293fs

c.878_881del · VCV4849450

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Leber congenital amaurosis 19

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -5.6, phastCons 1

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

Variant & gene context

Gene: USP45
Protein: p.Asp293fs
Coding: c.878_881del
MANE Select: NM_001346022
Type: Deletion
Location: chr6:99476195 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.28
Residue 293: the usp domain

Full USP45 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 19 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

USP45 p.His702fs Likely pathogenic ★ same condition
USP45 p.Lys311fs Likely pathogenic same condition
USP45 p.Gly570Glu Uncertain significance ★★ ⚠ same condition
USP45 p.Arg443Ter Likely pathogenic ★ same condition
USP45 p.Ser508Ter Pathogenic ★ same condition
USP45 c.377+5G>A Uncertain significance ★ same condition
USP45 p.Glu220Ter Conflicting classifications of pathogenicity ★ same condition
USP45 p.Lys546Ter Uncertain significance ★ 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/usp45-p-asp293fs (accessed [today's date]).

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