Is BUB1 p.Ala120Pro (c.358G>C) pathogenic?

BUB1 p.Ala120Pro (c.358G>C) is classified Uncertain significance in BUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-03). AlphaMissense: ambiguous (0.5522); Absent from gnomAD v4.1.

How common is BUB1 p.Ala120Pro (c.358G>C) in the general population?

BUB1 p.Ala120Pro (c.358G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BUB1 p.Ala120Pro (c.358G>C)?

AlphaMissense predicts ambiguous (score 0.5522) — an in-silico prediction, not a clinical call.

BUB1 p.Ala120Pro

c.358G>C · rs2468035817 · VCV1732983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5522 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5522	ambiguous
REVEL	0.308	indeterminate
SaProt	LLR -11.54	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	phastCons 0.99
Regional constraint	o/e 0.90	unconstrained · MANE · 40 kb · p 0.00043 · regional, not allelic
Overall
CADD	22.9	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: BUB1
Protein: p.Ala120Pro
Coding: c.358G>C
MANE Select: NM_004336
dbSNP: rs2468035817
Type: single nucleotide variant
Location: chr2:110672725 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.91 · 11 PDB
Residue 120: the bub1 n-terminal domain; the 'necessary for kinetochore localization' region; the 'necessary for interaction with knl1' region; an α-helix

Full BUB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BUB1 p.Ala120Gly Uncertain significance ★ ⚠ same residue
BUB1 p.Ala120Val Uncertain significance ★ ⚠ same residue
BUB1 c.1698+1G>T Uncertain significance ★★ same type
BUB1 p.Ala281Thr Uncertain significance ★★ ⚠ same type
BUB1 p.Ala283Thr Uncertain significance ★★ ⚠ same type
BUB1 p.Ala499Val Uncertain significance ★★ ⚠ same type
BUB1 p.Ala502Ser Uncertain significance ★★ ⚠ same type
BUB1 p.Ala630Gly 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/bub1-p-ala120pro (accessed [today's date]).

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