Is USP45 p.Val337fs (c.1008del) pathogenic?

USP45 p.Val337fs (c.1008del) is classified Benign/Likely benign in USP45 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-02). Rare (popmax 0.421%, nfe); Associated with retinal disorder.

What condition is associated with USP45 p.Val337fs (c.1008del)?

USP45 p.Val337fs (c.1008del) is associated with retinal disorder, inherited retinal dystrophy (ClinVar).

How common is USP45 p.Val337fs (c.1008del) in the general population?

USP45 p.Val337fs (c.1008del) is rare (popmax 0.421%, nfe) (gnomAD).

USP45 p.Val337fs

c.1008del · rs554927779 · VCV441010

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.421%, nfe)

Conditions

retinal disorder

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 10 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.8	GERP 0.94, phastCons 0.97
Overall
CADD	25.5	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 0.421% European (non-Finnish) · 4,932/1,170,488 alleles

Filtering AF 0.411% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.407%

Overall 0.333% 5,333/1,599,858 alleles · rare exomes 5,014/1,447,696 · genomes 319/152,162 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.73%	27
European (non-Finnish)grpmax	0.421%	237
Remaining individualsnot grpmax-eligible	0.271%	369
Finnishnot grpmax-eligible	0.0789%	1,267
African / African-American	0.0723%	1,384
Admixed American	0.0693%	1,444
Middle Eastern	0.0689%	1,451
South Asian	0.0536%	1,865
Ashkenazi Jewishnot grpmax-eligible	0.00681%	14,690

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: USP45
Protein: p.Val337fs
Coding: c.1008del
MANE Select: NM_001346022
dbSNP: rs554927779
Type: Deletion
Location: chr6:99468544 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.28
Residue 337: the usp domain

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

Disease context

retinal disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy

Similar variants

USP45 p.Arg2_Val3insTer Uncertain significance same condition
USP45 c.2073+1G>T Uncertain significance ★ same condition
USP45 p.Ala680Val Uncertain significance ★ ⚠ same condition
USP45 p.Glu220Ter Conflicting classifications of pathogenicity ★ same condition
USP45 p.Tyr598Ter Uncertain significance ★ same condition
USP45 p.Tyr730Ter Conflicting classifications of pathogenicity ★ same condition
USP45 p.Cys199Trp Uncertain significance ⚠ same condition
USP45 p.His114Arg 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-val337fs (accessed [today's date]).

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