Is USH2A p.Ser259fs (c.775_776del) pathogenic?

USH2A p.Ser259fs (c.775776del) is classified Pathogenic in USH2A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-11-04). No gnomAD frequency available for this variant; Associated with USH2A-related disorder.

What condition is associated with USH2A p.Ser259fs (c.775_776del)?

USH2A p.Ser259fs (c.775_776del) is associated with USH2A-related disorder, retinitis pigmentosa 39, inherited retinal dystrophy (ClinVar).

How common is USH2A p.Ser259fs (c.775_776del) in the general population?

USH2A p.Ser259fs (c.775_776del) is no gnomAD frequency available for this variant (gnomAD).

USH2A p.Ser259fs

c.775_776del · rs2038566220 · VCV866168

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 4 of 72
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.87	GERP -2.7, phastCons 0.001

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: USH2A
Protein: p.Ser259fs
Coding: c.775_776del
MANE Select: NM_206933
dbSNP: rs2038566220
Type: Microsatellite
Location: chr1:216364961 (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

Also linked: retinitis pigmentosa 39 inherited retinal dystrophy

Similar variants

USH2A p.Cys1447fs Pathogenic ★★★ same condition
USH2A p.Ile1183fs Likely pathogenic ★★★ same condition
USH2A c.852_853del Pathogenic ★★ same condition
USH2A p.Asn4079fs Pathogenic ★★ same condition
USH2A p.Asp3129fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Gln3959fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Glu3305fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Leu2973fs 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-ser259fs (accessed [today's date]).

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