Is BUB1B p.Ser83Cys (c.247A>T) pathogenic?

BUB1B p.Ser83Cys (c.247A>T) is classified Uncertain significance in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0777); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ser83Cys (c.247A>T)?

BUB1B p.Ser83Cys (c.247A>T) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Ser83Cys (c.247A>T) in the general population?

BUB1B p.Ser83Cys (c.247A>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about BUB1B p.Ser83Cys (c.247A>T)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

BUB1B p.Ser83Cys

c.247A>T · rs147832586 · VCV2592582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -3.66	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 3.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	23.0	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 0.005% Admixed American · 3/60,026 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,613,658 alleles · very rare exomes 3/1,461,300 · genomes 0/152,358 · 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: BUB1B
Protein: p.Ser83Cys
Coding: c.247A>T
MANE Select: NM_001211
dbSNP: rs147832586
Type: single nucleotide variant
Location: chr15:40170544 (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 83: the bub1 n-terminal domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BUB1B p.Ser83Arg Uncertain significance ★★ ⚠ same residue
BUB1B p.Ser83Gly Uncertain significance ★ ⚠ same residue
BUB1B p.Ser83Ile Uncertain significance ★ ⚠ same residue
BUB1B p.Ser83= Likely benign ★ same residue
BUB1B c.35+4G>T Uncertain significance ★★ same condition
BUB1B p.Ala1017Thr Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala1046Pro Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala108Thr Uncertain significance ★★ ⚠ 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-ser83cys (accessed [today's date]).

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