Is UBA3 p.Pro263His (c.788C>A) pathogenic?

UBA3 p.Pro263His (c.788C>A) is classified Uncertain significance in UBA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.6264); Very rare (popmax 0.00168%, amr).

How common is UBA3 p.Pro263His (c.788C>A) in the general population?

UBA3 p.Pro263His (c.788C>A) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about UBA3 p.Pro263His (c.788C>A)?

AlphaMissense predicts likely pathogenic (score 0.6264) — an in-silico prediction, not a clinical call.

UBA3 p.Pro263His

c.788C>A · VCV4601104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6264 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6264	likely pathogenic
REVEL	0.418	indeterminate
SaProt	LLR -12.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 25 kb · p 0.01 · regional, not allelic
Overall
CADD	29.3	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

Grpmax group 0.00168% Admixed American · 1/59,398 alleles

Filtering AF 0.000431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000314%

Overall 0.000685% 11/1,604,972 alleles · very rare exomes 9/1,452,832 · genomes 2/152,140 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,398
European (non-Finnish)	0.000852%	117,435

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: UBA3
Protein: p.Pro263His
Coding: c.788C>A
MANE Select: NM_003968
Type: single nucleotide variant
Location: chr3:69062085 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.20 · 13 PDB

Full UBA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBA3 c.20+7A>G Uncertain significance ★ same type
UBA3 p.Ala219Thr Uncertain significance ★ ⚠ same type
UBA3 p.Ala2Gly Uncertain significance ★ ⚠ same type
UBA3 p.Ala445Val Uncertain significance ★ ⚠ same type
UBA3 p.Arg116Gly Uncertain significance ★ ⚠ same type
UBA3 p.Arg157Gln Uncertain significance ★ ⚠ same type
UBA3 p.Arg94Thr Uncertain significance ★ ⚠ same type
UBA3 p.Asn152His Uncertain significance ★ ⚠ same type

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/uba3-p-pro263his (accessed [today's date]).

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