Is RDX p.Phe45Ser (c.134T>C) pathogenic?

RDX p.Phe45Ser (c.134T>C) is classified Uncertain significance in RDX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). AlphaMissense: likely pathogenic (0.9964); Absent from gnomAD v4.1; Associated with autosomal recessive nonsyndromic hearing loss 24.

What condition is associated with RDX p.Phe45Ser (c.134T>C)?

RDX p.Phe45Ser (c.134T>C) is associated with autosomal recessive nonsyndromic hearing loss 24 (ClinVar).

How common is RDX p.Phe45Ser (c.134T>C) in the general population?

RDX p.Phe45Ser (c.134T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RDX p.Phe45Ser (c.134T>C)?

AlphaMissense predicts likely pathogenic (score 0.9964) — an in-silico prediction, not a clinical call.

RDX p.Phe45Ser

c.134T>C · rs2539443649 · VCV3236793

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9964 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 24

Computational evidence

Protein change
AlphaMissense	0.9964	likely pathogenic · top 9% in RDX
REVEL	0.941	strongly pathogenic-leaning
SaProt	LLR -15.25	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 48 kb · p 0.00062 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RDX
Protein: p.Phe45Ser
Coding: c.134T>C
MANE Select: NM_002906
dbSNP: rs2539443649
Type: single nucleotide variant
Location: chr11:110264837 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 45: 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-phe45ser (accessed [today's date]).

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