Is RGR p.Arg274fs (c.820del) pathogenic?

RGR p.Arg274fs (c.820del) is classified Likely pathogenic in RGR (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). Absent from gnomAD; Associated with retinitis pigmentosa.

What condition is associated with RGR p.Arg274fs (c.820del)?

RGR p.Arg274fs (c.820del) is associated with retinitis pigmentosa (ClinVar).

How common is RGR p.Arg274fs (c.820del) in the general population?

RGR p.Arg274fs (c.820del) is absent from gnomAD (gnomAD).

How is Retinitis pigmentosa inherited?

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

RGR p.Arg274fs

c.820del · rs1589337745 · VCV802599

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.59	GERP 2.5

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: RGR
Protein: p.Arg274fs
Coding: c.820del
MANE Select: NM_153615 · reported on NM_001012720
dbSNP: rs1589337745
Type: Deletion
Location: chr10:84258583 (GRCh38)
Structure: AlphaFold pLDDT 62.88
Residue 274: the ras-gef domain

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

Disease context

retinitis pigmentosa — 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

RGR p.Arg274Ser Uncertain significance ★★ ⚠ same residue
RGR p.Ala234Thr Uncertain significance ★★ ⚠ same condition
RGR p.Arg289Gln Uncertain significance ★★ ⚠ same condition
RGR p.Asp154Asn Uncertain significance ★★ ⚠ same condition
RGR p.Gly87Ser Uncertain significance ★★ ⚠ same condition
RGR c.*416A>G Benign ★★ same condition
RGR c.*65A>G Benign ★★ same condition
RGR p.Ser241Phe Benign/Likely benign ★★ 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/rgr-p-arg274fs (accessed [today's date]).

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