Is RDX p.Arg342Cys (c.1024C>T) pathogenic?

RDX p.Arg342Cys (c.1024C>T) is classified Uncertain significance in RDX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-05). AlphaMissense: likely benign (0.274); Ultra-rare (popmax 0.0341%, mid); Associated with hearing loss disorder.

What condition is associated with RDX p.Arg342Cys (c.1024C>T)?

RDX p.Arg342Cys (c.1024C>T) is associated with hearing loss disorder (ClinVar).

How common is RDX p.Arg342Cys (c.1024C>T) in the general population?

RDX p.Arg342Cys (c.1024C>T) is ultra-rare (popmax 0.0341%, mid) (gnomAD).

What do computational predictors say about RDX p.Arg342Cys (c.1024C>T)?

AlphaMissense predicts likely benign (score 0.274) — an in-silico prediction, not a clinical call.

RDX p.Arg342Cys

c.1024C>T · rs1030064754 · VCV1065015

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.274 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0341%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hearing loss disorder

Computational evidence

Protein change
AlphaMissense	0.274	likely benign
REVEL	0.584	indeterminate
SaProt	LLR -12.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 48 kb · p 0.00062 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0341% Middle Eastern · 2/5,868 alleles

Filtering AF 0.006% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00249%

Overall 0.000995% 16/1,608,300 alleles · ultra-rare exomes 13/1,456,416 · genomes 3/151,884 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0341%	2,934
Admixed American	0.00337%	29,696
Finnishnot grpmax-eligible	0.00159%	62,870
European (non-Finnish)	0.000934%	107,038

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: RDX
Protein: p.Arg342Cys
Coding: c.1024C>T
MANE Select: NM_002906
dbSNP: rs1030064754
Type: single nucleotide variant
Location: chr11:110247769 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB

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

Disease context

hearing loss disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RDX p.Arg342His Uncertain significance ★★ ⚠ same residue
RDX p.Asp232Asn Uncertain significance ★★ same condition
RDX c.*156A>G Uncertain significance ★★ same type
RDX c.*2006A>G Uncertain significance ★★ same type
RDX c.*79A>C Uncertain significance ★★ same type
RDX p.Ala126Pro Uncertain significance ★★ ⚠ same type
RDX p.Ala442Thr Uncertain significance ★★ ⚠ same type
RDX p.Arg156Cys Uncertain significance ★★ ⚠ same type

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/rdx-p-arg342cys (accessed [today's date]).

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