Is DXO p.Arg319His (c.956G>A) pathogenic?

DXO p.Arg319His (c.956G>A) is classified Uncertain significance in DXO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely benign (0.088); Ultra-rare (popmax 0.033%, mid).

How common is DXO p.Arg319His (c.956G>A) in the general population?

DXO p.Arg319His (c.956G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about DXO p.Arg319His (c.956G>A)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

DXO p.Arg319His

c.956G>A · rs548465933 · VCV2507589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -9.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.65	GERP 0.46
Regional constraint	o/e 0.96	unconstrained · MANE · 1,795 bp · p 0.43 · regional, not allelic
Overall
CADD	16.78	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00663% 107/1,613,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0208%	4,808
East Asian	0.00891%	11,219
South Asian	0.00879%	11,383
Admixed American	0.00833%	12,001
European (non-Finnish)	0.00636%	15,733

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.Arg319His
Coding: c.956G>A
MANE Select: NM_005510
dbSNP: rs548465933
Type: single nucleotide variant
Location: chr6:31970196 (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-arg319his (accessed [today's date]).

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