Is BUB3 p.Val110Met (c.328G>A) pathogenic?

BUB3 p.Val110Met (c.328G>A) is classified Uncertain significance in BUB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-11). AlphaMissense: likely pathogenic (0.6872); Very rare (popmax 0.000169%, nfe).

How common is BUB3 p.Val110Met (c.328G>A) in the general population?

BUB3 p.Val110Met (c.328G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about BUB3 p.Val110Met (c.328G>A)?

AlphaMissense predicts likely pathogenic (score 0.6872) — an in-silico prediction, not a clinical call.

BUB3 p.Val110Met

c.328G>A · rs146410251 · VCV1729831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6872 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6872	likely pathogenic
REVEL	0.309	indeterminate
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 6,079 bp · p 8.5e-11 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,972 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,918 alleles · very rare

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: BUB3
Protein: p.Val110Met
Coding: c.328G>A
MANE Select: NM_004725
dbSNP: rs146410251
Type: single nucleotide variant
Location: chr10:123157791 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.10

Full BUB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BUB3 p.Val110Ala Uncertain significance ★ ⚠ same residue
BUB3 p.Val110= Likely benign ★ same residue
BUB3 p.Arg314= Likely benign ★★ same type
BUB3 p.Ser197= Likely benign ★★ same type
BUB3 p.Ser198= Likely benign ★★ same type
BUB3 p.Ala131Val Uncertain significance ★ ⚠ same type
BUB3 p.Ala155Val Uncertain significance ★ ⚠ same type
BUB3 p.Ala187Gly 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/bub3-p-val110met (accessed [today's date]).

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