Is BUB1B p.Ser1010Phe (c.3029C>T) pathogenic?

BUB1B p.Ser1010Phe (c.3029C>T) is classified Uncertain significance in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-02). AlphaMissense: likely benign (0.1122); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ser1010Phe (c.3029C>T)?

BUB1B p.Ser1010Phe (c.3029C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Ser1010Phe (c.3029C>T) in the general population?

BUB1B p.Ser1010Phe (c.3029C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about BUB1B p.Ser1010Phe (c.3029C>T)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

BUB1B p.Ser1010Phe

c.3029C>T · rs1367779530 · VCV1798991

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -8.98	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 1.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	16.06	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 0.00133% African / African-American · 1/74,928 alleles

Overall 0.000248% 4/1,614,084 alleles · very rare exomes 3/1,461,876 · genomes 1/152,208 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-Americangrpmax	0.00133%	74,928

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser1010Phe
Coding: c.3029C>T
MANE Select: NM_001211
dbSNP: rs1367779530
Type: single nucleotide variant
Location: chr15:40220635 (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 1010: the protein kinase domain

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.Ser1010Pro Uncertain significance ★★ ⚠ same residue
BUB1B p.Ser1010Thr Uncertain significance ★ ⚠ same residue
BUB1B p.Ser1010Cys 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-ser1010phe (accessed [today's date]).

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