Is RDX p.Ala264Pro (c.790G>C) pathogenic?

RDX p.Ala264Pro (c.790G>C) is classified Conflicting classifications of pathogenicity in RDX (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-01). AlphaMissense: likely pathogenic (0.9973); Rare (popmax 0.148%, sas).

How common is RDX p.Ala264Pro (c.790G>C) in the general population?

RDX p.Ala264Pro (c.790G>C) is rare (popmax 0.148%, sas) (gnomAD).

What do computational predictors say about RDX p.Ala264Pro (c.790G>C)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

RDX p.Ala264Pro

c.790G>C · rs201031650 · VCV229199

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic · top 7% in RDX
REVEL	0.808	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 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 48 kb · p 0.00062 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% South Asian · 132/88,980 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.016% 243/1,521,524 alleles · rare exomes 221/1,369,402 · genomes 22/152,122 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.148%	674
Middle Eastern	0.0571%	1,753
Remaining individualsnot grpmax-eligible	0.027%	3,710
Admixed American	0.0218%	4,592
East Asian	0.0136%	7,377
African / African-American	0.00685%	14,598
European (non-Finnish)	0.0062%	16,135

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.Ala264Pro
Coding: c.790G>C
MANE Select: NM_002906
dbSNP: rs201031650
Type: single nucleotide variant
Location: chr11:110255294 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 264: the ferm domain

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

Similar variants

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
RDX p.Ala442Thr Uncertain significance ★★ ⚠ same type
RDX p.Arg156Cys Uncertain significance ★★ ⚠ same type
RDX p.Arg342Cys Uncertain significance ★★ ⚠ same type
RDX p.Arg342His 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-ala264pro (accessed [today's date]).

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