Is BUB1B p.Ser157= (c.471A>C) pathogenic?

BUB1B p.Ser157= (c.471A>C) is classified Likely benign in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-01). Ultra-rare (popmax 0.0479%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ser157= (c.471A>C)?

BUB1B p.Ser157= (c.471A>C) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Ser157= (c.471A>C) in the general population?

BUB1B p.Ser157= (c.471A>C) is ultra-rare (popmax 0.0479%, nfe) (gnomAD).

BUB1B p.Ser157=

c.471A>C · rs2037225977 · VCV1742634

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0479%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.031	GERP -3, phastCons 0.022
Overall
CADD	7.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0479% European (non-Finnish) · 559/1,167,908 alleles

Filtering AF 0.0445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.0395% 632/1,600,256 alleles · ultra-rare exomes 632/1,448,140 · genomes 0/152,116 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0479%	2,089
Remaining individualsnot grpmax-eligible	0.042%	2,384
Middle Eastern	0.033%	3,030
African / African-American	0.0201%	4,977
Ashkenazi Jewishnot grpmax-eligible	0.017%	5,897
South Asian	0.0154%	6,487
Finnishnot grpmax-eligible	0.00941%	10,629
East Asian	0.00895%	11,178
Admixed American	0.00167%	59,950

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.Ser157=
Coding: c.471A>C
MANE Select: NM_001211
dbSNP: rs2037225977
Type: single nucleotide variant
Location: chr15:40176563 (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 157: 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

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

Similar variants

BUB1B p.Ser157Leu 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
BUB1B p.Ala171Pro Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala173Thr Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala183Thr 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-ser157 (accessed [today's date]).

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