Is BUB1B p.Arg120Gln (c.359G>A) pathogenic?

BUB1B p.Arg120Gln (c.359G>A) is classified Uncertain significance in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.6073); Very rare (popmax 0.0011%, nfe); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Arg120Gln (c.359G>A)?

BUB1B p.Arg120Gln (c.359G>A) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Arg120Gln (c.359G>A) in the general population?

BUB1B p.Arg120Gln (c.359G>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about BUB1B p.Arg120Gln (c.359G>A)?

AlphaMissense predicts likely pathogenic (score 0.6073) — an in-silico prediction, not a clinical call.

BUB1B p.Arg120Gln

c.359G>A · rs1349349252 · VCV950032

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6073 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
AlphaMissense	0.6073	likely pathogenic
REVEL	0.916	moderately pathogenic-leaning
SaProt	LLR -10.82	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	31.0	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 0.0011% European (non-Finnish) · 13/1,179,726 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.0013% 21/1,613,576 alleles · very rare exomes 21/1,461,386 · genomes 0/152,190 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,812
European (non-Finnish)grpmax	0.0011%	90,748

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg120Gln
Coding: c.359G>A
MANE Select: NM_001211
dbSNP: rs1349349252
Type: single nucleotide variant
Location: chr15:40170656 (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 120: the bub1 n-terminal domain; an α-helix

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.Arg120Ter Pathogenic ★★ same residue
BUB1B p.Arg120Gly Uncertain significance ★ ⚠ same residue
BUB1B p.Arg120Leu Uncertain significance ★ ⚠ same residue
BUB1B p.Arg114Ter 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

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-arg120gln (accessed [today's date]).

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