Is UBA2 p.Arg264Ser (c.792G>T) pathogenic?

UBA2 p.Arg264Ser (c.792G>T) is classified Uncertain significance in UBA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: ambiguous (0.4362); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with UBA2 p.Arg264Ser (c.792G>T)?

UBA2 p.Arg264Ser (c.792G>T) is associated with Inborn genetic diseases (ClinVar).

How common is UBA2 p.Arg264Ser (c.792G>T) in the general population?

UBA2 p.Arg264Ser (c.792G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about UBA2 p.Arg264Ser (c.792G>T)?

AlphaMissense predicts ambiguous (score 0.4362) — an in-silico prediction, not a clinical call.

UBA2 p.Arg264Ser

c.792G>T · VCV3976573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4362 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4362	ambiguous
REVEL	0.185	benign-leaning
SaProt	LLR -6.27	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.21	GERP -5.5, phastCons 0.86
Regional constraint	o/e 0.66	unconstrained · MANE · 25 kb · p 4.5e-13 · regional, not allelic
Overall
CADD	16.48	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 8.48e-05% European (non-Finnish) · 1/1,178,972 alleles

Overall 6.21e-05% 1/1,610,906 alleles · very rare exomes 1/1,458,660 · genomes 0/152,246 · 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: UBA2
Protein: p.Arg264Ser
Coding: c.792G>T
MANE Select: NM_005499
Type: single nucleotide variant
Location: chr19:34450285 (GRCh38)
Gene constraint: LOEUF 0.258 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.72 · 16 PDB
Residue 264: 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-arg264ser (accessed [today's date]).

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