Is USH2A p.Ile3055fs (c.9165_9168del) pathogenic?

USH2A p.Ile3055fs (c.91659168del) is classified Pathogenic in USH2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-05). Very rare (popmax 8.48e-05%, nfe); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Ile3055fs (c.9165_9168del)?

USH2A p.Ile3055fs (c.9165_9168del) is associated with Usher syndrome type 2A (ClinVar).

How common is USH2A p.Ile3055fs (c.9165_9168del) in the general population?

USH2A p.Ile3055fs (c.9165_9168del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

USH2A p.Ile3055fs

c.9165_9168del · rs2102821808 · VCV1069500

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 46 of 72
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,868 alleles

Overall 0.000124% 2/1,613,732 alleles · very rare exomes 2/1,461,472 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,930
European (non-Finnish)grpmax	8.48e-05%	1,179,869

Finnish 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: USH2A
Protein: p.Ile3055fs
Coding: c.9165_9168del
MANE Select: NM_206933
dbSNP: rs2102821808
Type: Microsatellite
Location: chr1:215844384 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3055: the fibronectin type-iii 17 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.Cys1447fs Pathogenic ★★★ same condition
USH2A p.Ile1183fs Likely pathogenic ★★★ same condition
USH2A c.850_853del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.852_853del Pathogenic ★★ same condition
USH2A p.Asn1379fs Pathogenic ★★ same condition
USH2A p.Asn2710fs Pathogenic ★★ same condition
USH2A p.Asn4079fs Pathogenic ★★ same condition
USH2A p.Asp3129fs 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-ile3055fs (accessed [today's date]).

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