Is BUB1B p.Ala173Val (c.518C>T) pathogenic?

BUB1B p.Ala173Val (c.518C>T) is classified Uncertain significance in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-06). AlphaMissense: likely benign (0.0747); Very rare (popmax 0.00223%, eas); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Ala173Val (c.518C>T)?

BUB1B p.Ala173Val (c.518C>T) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Ala173Val (c.518C>T) in the general population?

BUB1B p.Ala173Val (c.518C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BUB1B p.Ala173Val (c.518C>T)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

BUB1B p.Ala173Val

c.518C>T · rs552380700 · VCV855284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · 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	0.0747	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.99	GERP -4.2
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	1.81	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 · 1/44,848 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,986 alleles · very rare exomes 9/1,461,832 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,848
South Asian	0.0022%	45,543
European (non-Finnish)	0.000593%	168,569

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.Ala173Val
Coding: c.518C>T
MANE Select: NM_001211
dbSNP: rs552380700
Type: single nucleotide variant
Location: chr15:40176610 (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 173: the bub1 n-terminal domain; the 'necessary for interaction with knl1' region; 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.Ala173Thr Uncertain significance ★★ ⚠ same residue
BUB1B p.Ala173= Likely benign ★ 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

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-ala173val (accessed [today's date]).

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