Is RPGR p.Arg415= (c.1245G>A) pathogenic?

RPGR p.Arg415= (c.1245G>A) is classified Uncertain significance in RPGR (ClinVar, Single submitter, 2 submitters; last evaluated 2022-04-25). Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with RPGR p.Arg415= (c.1245G>A)?

RPGR p.Arg415= (c.1245G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is RPGR p.Arg415= (c.1245G>A) in the general population?

RPGR p.Arg415= (c.1245G>A) 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.Arg415=

c.1245G>A · rs2519828558 · VCV2130761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

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; conservation/SpliceAI carries the signal.
REVEL	0.638	indeterminate
Splicing
SpliceAI	Δ0.80	donor loss · deltas
Pangolin	Δ0.70	loss · gain 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Overall
CADD	18.28	PHRED · no single calibrated threshold — expert panels disagree

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.Arg415=
Coding: c.1245G>A
MANE Select: NM_001034853
dbSNP: rs2519828558
Type: single nucleotide variant
Location: chrX:38298956 (GRCh38)
Structure: AlphaFold pLDDT 56.59 · 3 PDB

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.Arg415Met Uncertain significance ★★ ⚠ same residue
RPGR p.Arg415fs Pathogenic ★★★ 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

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-arg415 (accessed [today's date]).

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