Is UBE2T p.Ala151Pro (c.451G>C) pathogenic?

UBE2T p.Ala151Pro (c.451G>C) is classified Uncertain significance in UBE2T (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-13). AlphaMissense: likely pathogenic (0.9597); Very rare (popmax 0.00225%, eas).

How common is UBE2T p.Ala151Pro (c.451G>C) in the general population?

UBE2T p.Ala151Pro (c.451G>C) is very rare (popmax 0.00225%, eas) (gnomAD).

What do computational predictors say about UBE2T p.Ala151Pro (c.451G>C)?

AlphaMissense predicts likely pathogenic (score 0.9597) — an in-silico prediction, not a clinical call.

UBE2T p.Ala151Pro

c.451G>C · VCV4928998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00225%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9597	likely pathogenic
REVEL	0.41	indeterminate
SaProt	LLR -16.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 3,916 bp · p 0.013 · regional, not allelic
Overall
CADD	27.9	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 0.00225% East Asian · 1/44,530 alleles

Overall 6.86e-05% 1/1,457,960 alleles · very rare

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: UBE2T
Protein: p.Ala151Pro
Coding: c.451G>C
MANE Select: NM_014176
Type: single nucleotide variant
Location: chr1:202333027 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI 0.08 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 13 PDB
Residue 151: the ubc core domain; the 'disordered' region; a β-strand

Full UBE2T gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBE2T p.Ala143Thr Uncertain significance ★★ ⚠ same type
UBE2T p.Cys24Tyr Uncertain significance ★★ ⚠ same type
UBE2T p.Gly170Val Uncertain significance ★★ ⚠ same type
UBE2T p.Pro58Ala Uncertain significance ★★ ⚠ same type
UBE2T p.Val187Ala Uncertain significance ★★ ⚠ same type
UBE2T c.385-11T>C Benign ★★ same type
UBE2T p.Ser5= Benign ★★ same type
UBE2T c.109+1G>A Likely pathogenic ★ 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/ube2t-p-ala151pro (accessed [today's date]).

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