Is USH2A p.Ser475fs (c.1421dup) pathogenic?

USH2A p.Ser475fs (c.1421dup) is classified Likely pathogenic in USH2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-25). No gnomAD frequency available for this variant; Associated with retinitis pigmentosa 39.

What condition is associated with USH2A p.Ser475fs (c.1421dup)?

USH2A p.Ser475fs (c.1421dup) is associated with retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Ser475fs (c.1421dup) in the general population?

USH2A p.Ser475fs (c.1421dup) is no gnomAD frequency available for this variant (gnomAD).

How is Retinitis pigmentosa inherited?

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

USH2A p.Ser475fs

c.1421dup · rs2527434040 · VCV2679516

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 8 of 72
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.91	GERP -1, 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.Ser475fs
Coding: c.1421dup
MANE Select: NM_206933
dbSNP: rs2527434040
Type: Duplication
Location: chr1:216323602 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 475: 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.Arg1504fs Pathogenic ★★★ same condition
USH2A p.Ala1214fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Ala1717fs Likely pathogenic ★★ same condition
USH2A p.Ala4678fs Pathogenic ★★ same condition
USH2A p.Arg1946fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Arg205fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Asn2377fs Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Asn443fs 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-ser475fs (accessed [today's date]).

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