Is UBA5 p.Pro140Arg (c.419C>G) pathogenic?

UBA5 p.Pro140Arg (c.419C>G) is classified Uncertain significance in UBA5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-11). AlphaMissense: likely pathogenic (0.7539); No allele count reported in gnomAD v4.1 (AN 1,474,138); Associated with developmental and epileptic encephalopathy, 44.

What condition is associated with UBA5 p.Pro140Arg (c.419C>G)?

UBA5 p.Pro140Arg (c.419C>G) is associated with developmental and epileptic encephalopathy, 44, spinocerebellar ataxia, autosomal recessive 24 (ClinVar).

How common is UBA5 p.Pro140Arg (c.419C>G) in the general population?

UBA5 p.Pro140Arg (c.419C>G) is no allele count reported in gnomAD v4.1 (AN 1,474,138) (gnomAD).

What do computational predictors say about UBA5 p.Pro140Arg (c.419C>G)?

AlphaMissense predicts likely pathogenic (score 0.7539) — an in-silico prediction, not a clinical call.

UBA5 p.Pro140Arg

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.419C>G · rs2530321320 · VCV2690405

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7539 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,474,138)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 44

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.7539	likely pathogenic
REVEL	0.689	pathogenic-leaning
SaProt	LLR -14.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 7,619 bp · p 0.0063 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,474,138). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: UBA5
Protein: p.Pro140Arg
Coding: c.419C>G
MANE Select: NM_024818
dbSNP: rs2530321320
Type: single nucleotide variant
Location: chr3:132670209 (GRCh38)

Full UBA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 44 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spinocerebellar ataxia, autosomal recessive 24

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

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/uba5-p-pro140arg (accessed [today's date]).

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