Is USH2A p.Gln299fs (c.895del) pathogenic?

USH2A p.Gln299fs (c.895del) is classified Pathogenic/Likely pathogenic in USH2A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-25). Very rare (popmax 0.00267%, afr); Associated with retinitis pigmentosa 39.

What condition is associated with USH2A p.Gln299fs (c.895del)?

USH2A p.Gln299fs (c.895del) is associated with retinitis pigmentosa 39, Usher syndrome type 2A, Usher syndrome (ClinVar).

How common is USH2A p.Gln299fs (c.895del) in the general population?

USH2A p.Gln299fs (c.895del) is very rare (popmax 0.00267%, 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.Gln299fs

c.895del · rs1338169194 · VCV438031

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, 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 4.1	GERP 0.026, phastCons 1
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,864 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00132% 2/152,048 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.Gln299fs
Coding: c.895del
MANE Select: NM_206933
dbSNP: rs1338169194
Type: Deletion
Location: chr1:216325553 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 299: 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

Also linked: Usher syndrome type 2A Usher syndrome

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.Gln299= Likely benign ★★ same residue
USH2A c.12295-?_14133+?del Likely pathogenic ★★★ same condition
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

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-gln299fs (accessed [today's date]).

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