Is RGR p.Ala2Val (c.5C>T) pathogenic?

RGR p.Ala2Val (c.5C>T) is classified Uncertain significance in RGR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.1542); Very rare (popmax 0.00223%, eas); Associated with inherited retinal dystrophy.

What condition is associated with RGR p.Ala2Val (c.5C>T)?

RGR p.Ala2Val (c.5C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is RGR p.Ala2Val (c.5C>T) in the general population?

RGR p.Ala2Val (c.5C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about RGR p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.1542) — an in-silico prediction, not a clinical call.

RGR p.Ala2Val

c.5C>T · rs1842730590 · VCV3028189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1542	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 4.8, phastCons 0.97
Overall
CADD	15.11	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,858 alleles

Overall 0.000137% 2/1,461,318 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,858
European (non-Finnish)	8.48e-05%	1,179,852

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.Ala2Val
Coding: c.5C>T
MANE Select: NM_153615 · reported on NM_001012720
dbSNP: rs1842730590
Type: single nucleotide variant
Location: chr10:84245095 (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.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
RGR p.Tyr153= Benign ★★ same condition
RGR c.744+5A>G Conflicting classifications of pathogenicity ★ 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-ala2val (accessed [today's date]).

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