Is DXO p.Arg294Cys (c.880C>T) pathogenic?

DXO p.Arg294Cys (c.880C>T) is classified Likely benign in DXO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely pathogenic (0.6444); Rare (popmax 0.559%, nfe).

How common is DXO p.Arg294Cys (c.880C>T) in the general population?

DXO p.Arg294Cys (c.880C>T) is rare (popmax 0.559%, nfe) (gnomAD).

What do computational predictors say about DXO p.Arg294Cys (c.880C>T)?

AlphaMissense predicts likely pathogenic (score 0.6444) — an in-silico prediction, not a clinical call.

DXO p.Arg294Cys

c.880C>T · VCV4083615

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6444 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.559%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6444	likely pathogenic
REVEL	0.697	pathogenic-leaning
SaProt	LLR -9.94	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,795 bp · p 0.43 · regional, not allelic
Overall
CADD	34.0	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 0.559% European (non-Finnish) · 6,596/1,180,004 alleles

Filtering AF 0.548% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.543%

Overall 0.434% 7,011/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.559%	179
Remaining individualsnot grpmax-eligible	0.229%	437
Admixed American	0.16%	625
Ashkenazi Jewishnot grpmax-eligible	0.159%	630
Finnishnot grpmax-eligible	0.0765%	1,307
African / African-American	0.0747%	1,339
East Asian	0.0334%	2,993
Middle Eastern	0.033%	3,031
South Asian	0.00769%	13,012

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: DXO
Protein: p.Arg294Cys
Coding: c.880C>T
MANE Select: NM_005510
Type: single nucleotide variant
Location: chr6:31970411 (GRCh38)
Gene constraint: LOEUF 1.264 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96

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

Similar variants

DXO p.Ala338Thr Uncertain significance ★ ⚠ same type
DXO p.Ala372Thr Uncertain significance ★ ⚠ same type
DXO p.Ala64Asp Uncertain significance ★ ⚠ same type
DXO p.Arg145Gln Uncertain significance ★ ⚠ same type
DXO p.Arg155Gly Uncertain significance ★ ⚠ same type
DXO p.Arg177Gln Uncertain significance ★ ⚠ same type
DXO p.Arg177Trp Uncertain significance ★ ⚠ same type
DXO p.Arg221Cys 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/dxo-p-arg294cys (accessed [today's date]).

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