Is RGR p.Pro45= (c.135G>A) pathogenic?

RGR p.Pro45= (c.135G>A) is classified Conflicting classifications of pathogenicity in RGR (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-03-26). Ultra-rare (popmax 0.0117%, amr); Associated with inherited retinal dystrophy.

What condition is associated with RGR p.Pro45= (c.135G>A)?

RGR p.Pro45= (c.135G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is RGR p.Pro45= (c.135G>A) in the general population?

RGR p.Pro45= (c.135G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

RGR p.Pro45=

c.135G>A · rs753086873 · VCV2968211

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.134	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -2.1
Overall
CADD	11.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,996 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00173% 28/1,613,982 alleles · ultra-rare exomes 23/1,461,894 · genomes 5/152,088 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,571
African / African-American	0.00534%	18,719
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Finnishnot grpmax-eligible	0.00469%	21,341
European (non-Finnish)	0.000932%	107,275

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: RGR
Protein: p.Pro45=
Coding: c.135G>A
MANE Select: NM_001012720
dbSNP: rs753086873
Type: single nucleotide variant
Location: chr10:84247646 (GRCh38)
Structure: AlphaFold pLDDT 62.88

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RGR p.Pro45Leu Uncertain significance ★ ⚠ same residue
RGR p.Pro45Ser Uncertain significance ★ ⚠ same residue
RGR p.Arg113Cys Uncertain significance ★★ ⚠ same condition
RGR p.Arg80His Uncertain significance ★★ ⚠ same condition
RGR p.Met199Val Uncertain significance ★★ ⚠ same condition
RGR p.Thr37Ile Uncertain significance ★★ ⚠ same condition
RGR p.Ser241Phe Benign/Likely benign ★★ same condition
RGR p.Thr9= 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-pro45 (accessed [today's date]).

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