Is RDX p.Ala321Val (c.962C>T) pathogenic?

RDX p.Ala321Val (c.962C>T) is classified Uncertain significance in RDX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: likely benign (0.3022); Very rare (popmax 0.000174%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RDX p.Ala321Val (c.962C>T)?

RDX p.Ala321Val (c.962C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RDX p.Ala321Val (c.962C>T) in the general population?

RDX p.Ala321Val (c.962C>T) is very rare (popmax 0.000174%, nfe) (gnomAD).

What do computational predictors say about RDX p.Ala321Val (c.962C>T)?

AlphaMissense predicts likely benign (score 0.3022) — an in-silico prediction, not a clinical call.

RDX p.Ala321Val

c.962C>T · VCV3431734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3022 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3022	likely benign
REVEL	0.522	indeterminate
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 48 kb · p 0.00062 · regional, not allelic
Overall
CADD	25.7	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 0.000174% European (non-Finnish) · 2/1,152,438 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000128% 2/1,557,774 alleles · very rare exomes 2/1,406,196 · genomes 0/151,578 · 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.Ala321Val
Coding: c.962C>T
MANE Select: NM_002906
Type: single nucleotide variant
Location: chr11:110247831 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 2 PDB
Residue 321: the 'disordered' region

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-ala321val (accessed [today's date]).

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