Is USP45 p.Phe377fs (c.1130del) pathogenic?

USP45 p.Phe377fs (c.1130del) is classified Uncertain significance in USP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). Associated with Leber congenital amaurosis.

What condition is associated with USP45 p.Phe377fs (c.1130del)?

USP45 p.Phe377fs (c.1130del) is associated with Leber congenital amaurosis (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.Phe377fs

c.1130del · VCV3780782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Leber congenital amaurosis

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 12 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP -1.9, phastCons 1

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

Variant & gene context

Gene: USP45
Protein: p.Phe377fs
Coding: c.1130del
MANE Select: NM_001346022
Type: Deletion
Location: chr6:99465114 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.28
Residue 377: the usp domain

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

Disease context

Leber congenital amaurosis — 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 c.2073+1G>T Uncertain significance ★ same condition
USP45 c.-10-2A>G Uncertain significance ★ same condition
USP45 p.Val337fs Benign/Likely benign ★★ same type
USP45 p.Asp293fs Likely pathogenic ★ same type
USP45 p.His702fs Likely pathogenic ★ same type
USP45 c.2314+14_2314+19del Likely benign ★ same type
USP45 p.Lys311fs Likely pathogenic same type
USP45 p.Arg2_Val3insTer Uncertain significance same type

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-phe377fs (accessed [today's date]).

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