Is BUB1 p.Gly970Val (c.2909G>T) pathogenic?

BUB1 p.Gly970Val (c.2909G>T) is classified Uncertain significance in BUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-15). AlphaMissense: likely pathogenic (0.6458); Very rare (popmax 0.00937%, afr).

How common is BUB1 p.Gly970Val (c.2909G>T) in the general population?

BUB1 p.Gly970Val (c.2909G>T) is very rare (popmax 0.00937%, afr) (gnomAD).

What do computational predictors say about BUB1 p.Gly970Val (c.2909G>T)?

AlphaMissense predicts likely pathogenic (score 0.6458) — an in-silico prediction, not a clinical call.

BUB1 p.Gly970Val

c.2909G>T · rs778192976 · VCV1797546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6458 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00937%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6458	likely pathogenic
REVEL	0.491	indeterminate
SaProt	LLR -11.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 40 kb · p 0.00043 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00937% African / African-American · 7/74,720 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000559% 9/1,610,054 alleles · very rare exomes 6/1,457,860 · genomes 3/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00937%	10,674
East Asian	0.00223%	44,850
Remaining individualsnot grpmax-eligible	0.0016%	62,332

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: BUB1
Protein: p.Gly970Val
Coding: c.2909G>T
MANE Select: NM_004336
dbSNP: rs778192976
Type: single nucleotide variant
Location: chr2:110641080 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.91 · 11 PDB
Residue 970: the protein kinase domain; an α-helix

Full BUB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BUB1 p.Gly970Ala Uncertain significance ★ same residue
BUB1 c.1698+1G>T Uncertain significance ★★ same type
BUB1 p.Ala281Thr Uncertain significance ★★ ⚠ same type
BUB1 p.Ala283Thr Uncertain significance ★★ ⚠ same type
BUB1 p.Ala499Val Uncertain significance ★★ ⚠ same type
BUB1 p.Ala502Ser Uncertain significance ★★ ⚠ same type
BUB1 p.Ala630Gly Uncertain significance ★★ ⚠ same type
BUB1 p.Ala705Thr Uncertain significance ★★ ⚠ same type

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/bub1-p-gly970val (accessed [today's date]).

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