Is RDX p.Pro471Ser (c.1411C>T) pathogenic?

RDX p.Pro471Ser (c.1411C>T) is classified Uncertain significance in RDX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-02). AlphaMissense: likely benign (0.1164); Ultra-rare (popmax 0.0165%, mid).

How common is RDX p.Pro471Ser (c.1411C>T) in the general population?

RDX p.Pro471Ser (c.1411C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about RDX p.Pro471Ser (c.1411C>T)?

AlphaMissense predicts likely benign (score 0.1164) — an in-silico prediction, not a clinical call.

RDX p.Pro471Ser

c.1411C>T · rs138560358 · VCV290799

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1164 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1164	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -8.72	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 48 kb · p 0.00062 · regional, not allelic
Overall
CADD	18.87	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0165% Middle Eastern · 1/6,074 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00341% 55/1,613,938 alleles · ultra-rare exomes 48/1,461,848 · genomes 7/152,090 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,074
African / African-American	0.00534%	18,721
European (non-Finnish)	0.00407%	24,584
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Pro471Ser
Coding: c.1411C>T
MANE Select: NM_002906
dbSNP: rs138560358
Type: single nucleotide variant
Location: chr11:110233413 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 471: the 'disordered' region

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

Similar variants

RDX p.Pro471Ala Uncertain significance ★★ ⚠ same residue
RDX p.Pro471= Conflicting classifications of pathogenicity ★ same residue
RDX p.Pro471His Uncertain significance ★ ⚠ same residue
RDX p.Pro471Thr Uncertain significance ★ ⚠ same residue
RDX c.*156A>G Uncertain significance ★★ same type
RDX c.*2006A>G Uncertain significance ★★ same type
RDX c.*79A>C Uncertain significance ★★ same type
RDX p.Ala126Pro Uncertain significance ★★ ⚠ same type

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-pro471ser (accessed [today's date]).

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