Is USH2A p.Ala73fs (c.218del) pathogenic?

USH2A p.Ala73fs (c.218del) is classified Likely pathogenic in USH2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-08). Associated with USH2A-related disorder.

What condition is associated with USH2A p.Ala73fs (c.218del)?

USH2A p.Ala73fs (c.218del) is associated with USH2A-related disorder (ClinVar).

USH2A p.Ala73fs

c.218del · VCV4940320

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

USH2A-related 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 2 of 72
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.1	GERP -2.5

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

Variant & gene context

Gene: USH2A
Protein: p.Ala73fs
Coding: c.218del
MANE Select: NM_206933
Type: Deletion
Location: chr1:216422119 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Disease context

USH2A-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USH2A p.Ala2311fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Arg2509fs Pathogenic ★★ same condition
USH2A p.Arg4137fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Asn405fs Pathogenic ★★ same condition
USH2A p.Asn960fs Pathogenic ★★ same condition
USH2A p.Asp4448_Ser4449del Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Cys768fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Glu2054fs 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-ala73fs (accessed [today's date]).

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