Is UBA2 p.Ser577Cys (c.1730C>G) pathogenic?

UBA2 p.Ser577Cys (c.1730C>G) is classified Uncertain significance in UBA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: ambiguous (0.522); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with UBA2 p.Ser577Cys (c.1730C>G)?

UBA2 p.Ser577Cys (c.1730C>G) is associated with Inborn genetic diseases (ClinVar).

How common is UBA2 p.Ser577Cys (c.1730C>G) in the general population?

UBA2 p.Ser577Cys (c.1730C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UBA2 p.Ser577Cys (c.1730C>G)?

AlphaMissense predicts ambiguous (score 0.522) — an in-silico prediction, not a clinical call.

UBA2 p.Ser577Cys

c.1730C>G · VCV3976577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.522 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.522	ambiguous
REVEL	0.147	moderately benign-leaning
SaProt	LLR -10.11	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 25 kb · p 4.5e-13 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UBA2
Protein: p.Ser577Cys
Coding: c.1730C>G
MANE Select: NM_005499
Type: single nucleotide variant
Location: chr19:34467003 (GRCh38)
Gene constraint: LOEUF 0.258 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.72 · 16 PDB
Residue 577: the 'disordered' region; a UniProt-annotated variant site (in acces)

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-ser577cys (accessed [today's date]).

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