Is BUB1B p.Ile807Val (c.2419A>G) pathogenic?

BUB1B p.Ile807Val (c.2419A>G) is classified Uncertain significance in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-13). AlphaMissense: likely benign (0.0993); Very rare (popmax 0.00223%, eas); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Ile807Val (c.2419A>G)?

BUB1B p.Ile807Val (c.2419A>G) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Ile807Val (c.2419A>G) in the general population?

BUB1B p.Ile807Val (c.2419A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BUB1B p.Ile807Val (c.2419A>G)?

AlphaMissense predicts likely benign (score 0.0993) — an in-silico prediction, not a clinical call.

BUB1B p.Ile807Val

c.2419A>G · rs2542575332 · VCV2721193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
AlphaMissense	0.0993	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.36	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 4.2	GERP 0.97, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	17.93	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 0.00223% East Asian · 1/44,816 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,152 alleles · very rare exomes 3/1,460,828 · genomes 0/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,816
European (non-Finnish)	0.00017%	589,661

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: BUB1B
Protein: p.Ile807Val
Coding: c.2419A>G
MANE Select: NM_001211
dbSNP: rs2542575332
Type: single nucleotide variant
Location: chr15:40212532 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.62 · 9 PDB
Residue 807: the protein kinase domain

Full BUB1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mosaic variegated aneuploidy syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BUB1B p.Ile807Met Uncertain significance ★ ⚠ same residue
BUB1B p.Arg114Ter Pathogenic ★★ same condition
BUB1B p.Arg120Ter Pathogenic ★★ same condition
BUB1B p.Arg194Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Arg199Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Arg67Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Gln267Ter Pathogenic ★★ same condition
BUB1B p.Leu737Ter Pathogenic/Likely pathogenic ★★ 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/bub1b-p-ile807val (accessed [today's date]).

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