Is RPGR p.Glu774Ter (c.2320G>T) pathogenic?

RPGR p.Glu774Ter (c.2320G>T) is classified Pathogenic in RPGR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with RPGR p.Glu774Ter (c.2320G>T)?

RPGR p.Glu774Ter (c.2320G>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is RPGR p.Glu774Ter (c.2320G>T) in the general population?

RPGR p.Glu774Ter (c.2320G>T) is absent from gnomAD v4.1 (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

RPGR p.Glu774Ter

c.2320G>T · rs2067186077 · VCV2081066

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (15 of 15) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	26.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RPGR
Protein: p.Glu774Ter
Coding: c.2320G>T
MANE Select: NM_001034853
dbSNP: rs2067186077
Type: single nucleotide variant
Location: chrX:38286679 (GRCh38)
Structure: AlphaFold pLDDT 56.59 · 3 PDB
Residue 774: the 'disordered' region

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

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

RPGR p.Ser774fs Uncertain significance ★ same residue
RPGR c.1245+3A>G Pathogenic ★★★ same condition
RPGR c.1572+1G>A Pathogenic ★★★ same condition
RPGR c.1573-1G>A Pathogenic ★★★ same condition
RPGR c.1573-8A>G Likely pathogenic ★★★ same condition
RPGR c.1754-3C>G Pathogenic ★★★ same condition
RPGR c.247+5G>A Pathogenic ★★★ same condition
RPGR c.310+1G>C 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/rpgr-p-glu774ter (accessed [today's date]).

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