Is BUB1B p.Ser83= (c.249C>T) pathogenic?

BUB1B p.Ser83= (c.249C>T) is classified Likely benign in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). Very rare (popmax 0.00878%, sas); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ser83= (c.249C>T)?

BUB1B p.Ser83= (c.249C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Ser83= (c.249C>T) in the general population?

BUB1B p.Ser83= (c.249C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

BUB1B p.Ser83=

c.249C>T · rs576848032 · VCV1792176

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.52	GERP -3.1, phastCons 0.001
Overall
CADD	10.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,072 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00062% 10/1,613,562 alleles · very rare exomes 9/1,461,244 · genomes 1/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,384
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Ser83=
Coding: c.249C>T
MANE Select: NM_001211
dbSNP: rs576848032
Type: single nucleotide variant
Location: chr15:40170546 (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.Ser83Cys Uncertain significance ★ ⚠ same residue
BUB1B p.Ser83Gly Uncertain significance ★ ⚠ same residue
BUB1B p.Ser83Ile Uncertain significance ★ ⚠ 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-ser83 (accessed [today's date]).

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