Is BUB1 p.Ile31Val (c.91A>G) pathogenic?

BUB1 p.Ile31Val (c.91A>G) is classified Uncertain significance in BUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: likely benign (0.0877); Very rare (popmax 8.5e-05%, nfe).

How common is BUB1 p.Ile31Val (c.91A>G) in the general population?

BUB1 p.Ile31Val (c.91A>G) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about BUB1 p.Ile31Val (c.91A>G)?

AlphaMissense predicts likely benign (score 0.0877) — an in-silico prediction, not a clinical call.

BUB1 p.Ile31Val

c.91A>G · rs2468038798 · VCV3224131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0877 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0877	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.84	phastCons 0.7
Regional constraint	o/e 0.90	unconstrained · MANE · 40 kb · p 0.00043 · regional, not allelic
Overall
CADD	10.74	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 8.5e-05% European (non-Finnish) · 1/1,176,408 alleles

Overall 6.21e-05% 1/1,609,762 alleles · very rare exomes 1/1,457,430 · genomes 0/152,332 · joint denominator

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: BUB1
Protein: p.Ile31Val
Coding: c.91A>G
MANE Select: NM_004336
dbSNP: rs2468038798
Type: single nucleotide variant
Location: chr2:110674220 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.91 · 11 PDB
Residue 31: the bub1 n-terminal domain; the 'necessary for kinetochore localization' region; an α-helix

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

Similar variants

BUB1 p.Ile31Leu Uncertain significance ★ ⚠ same residue
BUB1 p.Ile31= Likely benign ★ 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-ile31val (accessed [today's date]).

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