Is RDX p.Phe85Ile (c.253T>A) pathogenic?

RDX p.Phe85Ile (c.253T>A) is classified Uncertain significance in RDX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-12). AlphaMissense: likely pathogenic (0.932); Very rare (popmax 0.00535%, afr); Associated with Inborn genetic diseases.

What condition is associated with RDX p.Phe85Ile (c.253T>A)?

RDX p.Phe85Ile (c.253T>A) is associated with Inborn genetic diseases (ClinVar).

How common is RDX p.Phe85Ile (c.253T>A) in the general population?

RDX p.Phe85Ile (c.253T>A) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about RDX p.Phe85Ile (c.253T>A)?

AlphaMissense predicts likely pathogenic (score 0.932) — an in-silico prediction, not a clinical call.

RDX p.Phe85Ile

c.253T>A · VCV4152260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.932	likely pathogenic
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -13.39	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	29.8	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 0.00535% African / African-American · 4/74,812 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,611,182 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,703
Admixed American	0.00334%	29,976
European (non-Finnish)	8.49e-05%	1,177,559

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.Phe85Ile
Coding: c.253T>A
MANE Select: NM_002906
Type: single nucleotide variant
Location: chr11:110264174 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 85: 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-phe85ile (accessed [today's date]).

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