Is USH2A p.Arg4040fs (c.12118del) pathogenic?

USH2A p.Arg4040fs (c.12118del) is classified Likely pathogenic in USH2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-16). Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Arg4040fs (c.12118del)?

USH2A p.Arg4040fs (c.12118del) is associated with Usher syndrome type 2A (ClinVar).

USH2A p.Arg4040fs

c.12118del · VCV4817081

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Usher syndrome type 2A

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 62 of 72
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.086	GERP -2.2, phastCons 0.001

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

Variant & gene context

Gene: USH2A
Protein: p.Arg4040fs
Coding: c.12118del
MANE Select: NM_206933
Type: Deletion
Location: chr1:215680325 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4040: the fibronectin type-iii 25 domain

Full USH2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USH2A p.Arg4040Cys Uncertain significance ★★ ⚠ same residue
USH2A c.11389+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.11549del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.4251+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.4758+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.7594+2del Likely pathogenic ★★ same condition
USH2A c.9055+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Ala1312fs Pathogenic/Likely pathogenic ★★ 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/ush2a-p-arg4040fs (accessed [today's date]).

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