Is UBA2 p.Arg320Cys (c.958C>T) pathogenic?

UBA2 p.Arg320Cys (c.958C>T) is classified Uncertain significance in UBA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.0608); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with UBA2 p.Arg320Cys (c.958C>T)?

UBA2 p.Arg320Cys (c.958C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UBA2 p.Arg320Cys (c.958C>T) in the general population?

UBA2 p.Arg320Cys (c.958C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about UBA2 p.Arg320Cys (c.958C>T)?

AlphaMissense predicts likely benign (score 0.0608) — an in-silico prediction, not a clinical call.

UBA2 p.Arg320Cys

c.958C>T · VCV3976572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0608 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0608	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -10.08	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -5.1
Regional constraint	o/e 0.66	unconstrained · MANE · 25 kb · p 4.5e-13 · regional, not allelic
Overall
CADD	17.88	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 0.00446% East Asian · 2/44,826 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000807% 13/1,610,744 alleles · very rare exomes 10/1,458,750 · genomes 3/151,994 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,413
South Asian	0.0022%	45,387
Admixed American	0.00167%	59,890
African / African-American	0.00134%	74,830
European (non-Finnish)	0.000594%	168,249

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: UBA2
Protein: p.Arg320Cys
Coding: c.958C>T
MANE Select: NM_005499
Type: single nucleotide variant
Location: chr19:34452067 (GRCh38)
Gene constraint: LOEUF 0.258 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.72 · 16 PDB
Residue 320: a UniProt-annotated variant site (in acces); an α-helix

Full UBA2 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

UBA2 p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
UBA2 p.Arg274Trp Uncertain significance ★★ ⚠ same condition
UBA2 p.Ile468Leu Uncertain significance ★★ ⚠ same condition
UBA2 p.Ala121Thr Uncertain significance ★ ⚠ same condition
UBA2 p.Ala215Val Uncertain significance ★ ⚠ same condition
UBA2 p.Ala296Val Uncertain significance ★ ⚠ same condition
UBA2 p.Ala559Thr Uncertain significance ★ ⚠ same condition
UBA2 p.Ala622Gly 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/uba2-p-arg320cys (accessed [today's date]).

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