Is UBA2 p.Ala296Val (c.887C>T) pathogenic?

UBA2 p.Ala296Val (c.887C>T) is classified Uncertain significance in UBA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.0598); Ultra-rare (popmax 0.0207%, sas); Associated with Inborn genetic diseases.

What condition is associated with UBA2 p.Ala296Val (c.887C>T)?

UBA2 p.Ala296Val (c.887C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UBA2 p.Ala296Val (c.887C>T) in the general population?

UBA2 p.Ala296Val (c.887C>T) is ultra-rare (popmax 0.0207%, sas) (gnomAD).

What do computational predictors say about UBA2 p.Ala296Val (c.887C>T)?

AlphaMissense predicts likely benign (score 0.0598) — an in-silico prediction, not a clinical call.

UBA2 p.Ala296Val

c.887C>T · rs113242502 · VCV2382749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0598 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0207%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0598	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.92	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 0.97	GERP 1.9, phastCons 0.99
Regional constraint	o/e 0.66	unconstrained · MANE · 25 kb · p 4.5e-13 · regional, not allelic
Overall
CADD	17.71	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 0.0207% South Asian · 17/82,262 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.00529% 83/1,568,260 alleles · ultra-rare exomes 73/1,416,222 · genomes 10/152,038 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0207%	4,839
Remaining individualsnot grpmax-eligible	0.0182%	5,491
Middle Eastern	0.0171%	5,852
African / African-American	0.00953%	10,488
European (non-Finnish)	0.00398%	25,124
Admixed American	0.00183%	54,680

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.Ala296Val
Coding: c.887C>T
MANE Select: NM_005499
dbSNP: rs113242502
Type: single nucleotide variant
Location: chr19:34451996 (GRCh38)
Gene constraint: LOEUF 0.258 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.72 · 16 PDB
Residue 296: 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.Ala559Thr Uncertain significance ★ ⚠ same condition
UBA2 p.Ala622Gly Uncertain significance ★ ⚠ same condition
UBA2 p.Ala87Pro 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-ala296val (accessed [today's date]).

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