Is USH2A c.9959del pathogenic?

USH2A c.9959del is classified Likely pathogenic in USH2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-23). Very rare (popmax 8.48e-05%, nfe); Associated with retinitis pigmentosa 39.

What condition is associated with USH2A c.9959del?

USH2A c.9959del is associated with retinitis pigmentosa 39 (ClinVar).

How common is USH2A c.9959del in the general population?

USH2A c.9959del is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

USH2A c.9959del

rs2464420459 · VCV3240703

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

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

Conditions

retinitis pigmentosa 39

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.091	GERP -3, phastCons 0.55
Non-coding constraint	Z 1.52	1 kb window · o/e 0.89 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,910 alleles

Overall 6.2e-05% 1/1,613,772 alleles · very rare exomes 1/1,461,468 · genomes 0/152,304 · joint denominator

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
Coding: c.9959del
MANE Select: NM_206933
dbSNP: rs2464420459
Type: Deletion
Location: chr1:215790282 (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

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 c.11389+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.11549del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.4251+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.4758+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.486-4_486-2del Likely pathogenic ★★ same condition
USH2A c.7594+2del Likely pathogenic ★★ same condition
USH2A c.9055+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Ala2311fs 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-c-9959del (accessed [today's date]).

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