Is RDX p.Phe44Cys (c.131T>G) pathogenic?

RDX p.Phe44Cys (c.131T>G) is classified Uncertain significance in RDX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely pathogenic (0.9874); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RDX p.Phe44Cys (c.131T>G)?

RDX p.Phe44Cys (c.131T>G) is associated with Inborn genetic diseases (ClinVar).

How common is RDX p.Phe44Cys (c.131T>G) in the general population?

RDX p.Phe44Cys (c.131T>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about RDX p.Phe44Cys (c.131T>G)?

AlphaMissense predicts likely pathogenic (score 0.9874) — an in-silico prediction, not a clinical call.

RDX p.Phe44Cys

c.131T>G · rs1859958324 · VCV2274857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9874	likely pathogenic
REVEL	0.839	moderately pathogenic-leaning
SaProt	LLR -13.55	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	31.0	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,974 alleles

Overall 6.2e-05% 1/1,613,978 alleles · very rare exomes 1/1,461,746 · genomes 0/152,232 · joint denominator

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.Phe44Cys
Coding: c.131T>G
MANE Select: NM_002906
dbSNP: rs1859958324
Type: single nucleotide variant
Location: chr11:110264840 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 44: the ferm domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RDX p.Ala126Pro Uncertain significance ★★ ⚠ same condition
RDX p.Ala442Thr Uncertain significance ★★ ⚠ same condition
RDX p.Arg156Cys Uncertain significance ★★ ⚠ same condition
RDX p.Arg342His Uncertain significance ★★ ⚠ same condition
RDX p.Arg523His Uncertain significance ★★ ⚠ same condition
RDX p.Asn138Ser Uncertain significance ★★ ⚠ same condition
RDX p.Asn277Ser Uncertain significance ★★ ⚠ same condition
RDX p.Glu385Ala 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-phe44cys (accessed [today's date]).

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