Is RDX p.Ala282= (c.846C>T) pathogenic?

RDX p.Ala282= (c.846C>T) is classified Likely benign in RDX (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-09). Ultra-rare (popmax 0.0347%, afr).

How common is RDX p.Ala282= (c.846C>T) in the general population?

RDX p.Ala282= (c.846C>T) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

RDX p.Ala282=

c.846C>T · rs368983071 · VCV3044989

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP -5.2, phastCons 0.004
Overall
CADD	7.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0347% African / African-American · 26/74,994 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00279% 45/1,613,676 alleles · ultra-rare exomes 37/1,461,440 · genomes 8/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,884
Middle Eastern	0.033%	3,027
Remaining individualsnot grpmax-eligible	0.008%	12,496
Admixed American	0.00167%	59,948
South Asian	0.0011%	91,074
European (non-Finnish)	0.000848%	117,981

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.Ala282=
Coding: c.846C>T
MANE Select: NM_002906
dbSNP: rs368983071
Type: single nucleotide variant
Location: chr11:110254059 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 282: 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-ala282 (accessed [today's date]).

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