Is RDX p.Pro472fs (c.1412dup) pathogenic?

RDX p.Pro472fs (c.1412dup) is classified Likely pathogenic in RDX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). Very rare (popmax 0.000763%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 24.

What condition is associated with RDX p.Pro472fs (c.1412dup)?

RDX p.Pro472fs (c.1412dup) is associated with autosomal recessive nonsyndromic hearing loss 24 (ClinVar).

How common is RDX p.Pro472fs (c.1412dup) in the general population?

RDX p.Pro472fs (c.1412dup) is very rare (popmax 0.000763%, nfe) (gnomAD).

RDX p.Pro472fs

c.1412dup · VCV4845838

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Conditions

autosomal recessive nonsyndromic hearing loss 24

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 13 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.38	GERP -0.097, phastCons 0.63
Region caveats
Repeat context	tandem	(TGG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,914 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000684% 10/1,461,798 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,004
European (non-Finnish)grpmax	0.000763%	131,102

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro472fs
Coding: c.1412dup
MANE Select: NM_002906
Type: Duplication
Location: chr11:110233411 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 472: the 'disordered' region

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

Disease context

autosomal recessive nonsyndromic hearing loss 24 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RDX p.Ala469fs Pathogenic same condition
RDX p.Ile359fs Pathogenic/Likely pathogenic ★★ same condition
RDX p.Lys438fs Pathogenic ★★ same condition
RDX p.Trp242fs Pathogenic ★★ same condition
RDX c.*156A>G Uncertain significance ★★ same condition
RDX c.*2006A>G Uncertain significance ★★ same condition
RDX c.*79A>C Uncertain significance ★★ same condition
RDX p.Arg350His Uncertain significance ★★ ⚠ 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/rdx-p-pro472fs (accessed [today's date]).

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