Is RDX p.Pro118= (c.354G>T) pathogenic?

RDX p.Pro118= (c.354G>T) is classified Conflicting classifications of pathogenicity in RDX (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-15). Rare (popmax 0.744%, eas); Associated with autosomal recessive nonsyndromic hearing loss 24.

What condition is associated with RDX p.Pro118= (c.354G>T)?

RDX p.Pro118= (c.354G>T) is associated with autosomal recessive nonsyndromic hearing loss 24 (ClinVar).

How common is RDX p.Pro118= (c.354G>T) in the general population?

RDX p.Pro118= (c.354G>T) is rare (popmax 0.744%, eas) (gnomAD).

RDX p.Pro118=

c.354G>T · rs144543614 · VCV165054

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.744%, eas)

Conditions

autosomal recessive nonsyndromic hearing loss 24

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -5.2, phastCons 0.001
Overall
CADD	3.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.744% East Asian · 334/44,882 alleles

Filtering AF 0.678% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.653%

Overall 0.0376% 606/1,613,698 alleles · rare exomes 532/1,461,530 · genomes 74/152,168 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.744%	134
Ashkenazi Jewishnot grpmax-eligible	0.476%	210
Remaining individualsnot grpmax-eligible	0.088%	1,136
South Asian	0.0571%	1,751
Middle Eastern	0.0165%	6,058
European (non-Finnish)	0.00186%	53,624
Admixed American	0.00167%	59,980

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.Pro118=
Coding: c.354G>T
MANE Select: NM_002906
dbSNP: rs144543614
Type: single nucleotide variant
Location: chr11:110264073 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 118: the ferm domain

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 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
RDX p.Asn502Asp Uncertain significance ★★ ⚠ same condition
RDX p.Lys526Arg Uncertain significance ★★ ⚠ same condition
RDX p.Pro471Ala Uncertain significance ★★ ⚠ same condition
RDX p.Ser501Pro 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-pro118 (accessed [today's date]).

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