Is BUB1B p.Ser16= (c.48C>T) pathogenic?

BUB1B p.Ser16= (c.48C>T) is classified Likely benign in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-07). Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ser16= (c.48C>T)?

BUB1B p.Ser16= (c.48C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Ser16= (c.48C>T) in the general population?

BUB1B p.Ser16= (c.48C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

BUB1B p.Ser16=

c.48C>T · rs1369704386 · VCV1743949

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -2.2	GERP -4.5
Overall
CADD	4.632	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,892 alleles

Overall 0.000124% 2/1,613,912 alleles · very rare exomes 1/1,461,880 · genomes 1/152,032 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,892
European (non-Finnish)	8.47e-05%	1,180,018

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.Ser16=
Coding: c.48C>T
MANE Select: NM_001211
dbSNP: rs1369704386
Type: single nucleotide variant
Location: chr15:40165065 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.62 · 9 PDB

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.Ser16Cys Uncertain significance ★ ⚠ same residue
BUB1B p.Ser16Tyr Uncertain significance ★ ⚠ same residue
BUB1B p.Ser16Phe 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

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-ser16 (accessed [today's date]).

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