RPGR p.Pro367fs
c.1100del · rs62635000 · VCV98728
ClinGen expert panel — X-linked Inherited Retinal Disease VCEP
Pathogenic for RPGR-related retinopathy. Applied ACMG criteria (verbatim):
PVS1 PM2_Supporting PS4_Supporting
Curation rationale (ClinGen, verbatim)
NM_001034853.2(RPGR):c.1100del (p.Pro367LeufsTer14) is a frameshift variant due to deletion of 1 nucleotide and introduces a premature stop codon after 14 amino acids in exon 10 of 15 that is predicted to result in nonsense-mediated decay (PVS1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). This variant has been reported in at least 2 apparently unrelated probands meeting one of the PS4 requirements of a male with some functional vision impairment by age 30 years and/or decreased or absent electroretinogram responses, or a female with functional visual abnormality and documentation of a male relative affected with retinitis pigmentosa (PMID: 36017691, PMID: 10937588, PS4_Supporting). In summary, this variant is classified as pathogenic for RPGR-related retinopathy based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0; PVS1, PS4_Supporting and PM2_Supporting. (date of approval 05/16/2025).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 10 of 15 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.29 | GERP -3.1, phastCons 0.32 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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
- RPGR
- Protein
- p.Pro367fs
- Coding
- c.1100del
- MANE Select
- NM_001034853
- dbSNP
- rs62635000
- Type
- Deletion
- Location
- chrX:38299101 (GRCh38)
- Structure
- AlphaFold pLDDT 56.59 · 3 PDB
- Residue 367
- a β-strand
Similar variants
- RPGR p.Pro367Ala Likely benign ★★★ ⚠ same residue
- RPGR p.Pro367del Uncertain significance ★★ same residue
- RPGR p.Pro367Ser Uncertain significance ★ ⚠ same residue
- RPGR c.154+3_154+6del Pathogenic ★★★ same condition
- RPGR c.1572+1del Likely pathogenic ★★★ same condition
- RPGR p.Glu1000fs Pathogenic ★★★ same condition
- RPGR p.Glu1010fs Pathogenic ★★★ same condition
- RPGR p.Glu1012fs 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/rpgr-p-pro367fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown