Is USH2A p.Ser343fs (c.1026_1029del) pathogenic?

USH2A p.Ser343fs (c.10261029del) is classified Pathogenic in USH2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-31). Very rare (popmax 0.00133%, afr); Associated with retinitis pigmentosa 39.

What condition is associated with USH2A p.Ser343fs (c.1026_1029del)?

USH2A p.Ser343fs (c.1026_1029del) is associated with retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Ser343fs (c.1026_1029del) in the general population?

USH2A p.Ser343fs (c.1026_1029del) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

USH2A p.Ser343fs

c.1026_1029del · rs1458938381 · VCV1457186

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

retinitis pigmentosa 39

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 6 of 72
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,024 alleles

Overall 6.84e-05% 1/1,461,666 alleles · very rare

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.Ser343fs
Coding: c.1026_1029del
MANE Select: NM_206933
dbSNP: rs1458938381
Type: Microsatellite
Location: chr1:216325419 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 343: the laminin n-terminal domain

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

Disease context

retinitis pigmentosa 39 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

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-ser343fs (accessed [today's date]).

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