Is BUB3 p.Ala131Val (c.392C>T) pathogenic?

BUB3 p.Ala131Val (c.392C>T) is classified Uncertain significance in BUB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: ambiguous (0.4114); Very rare (popmax 0.0011%, sas).

How common is BUB3 p.Ala131Val (c.392C>T) in the general population?

BUB3 p.Ala131Val (c.392C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BUB3 p.Ala131Val (c.392C>T)?

AlphaMissense predicts ambiguous (score 0.4114) — an in-silico prediction, not a clinical call.

BUB3 p.Ala131Val

c.392C>T · rs2493759984 · VCV1736252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4114	ambiguous
REVEL	0.201	benign-leaning
SaProt	LLR -5.41	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	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	21.2	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 0.0011% South Asian · 1/90,882 alleles

Overall 6.84e-05% 1/1,461,246 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.Ala131Val
Coding: c.392C>T
MANE Select: NM_004725
dbSNP: rs2493759984
Type: single nucleotide variant
Location: chr10:123157855 (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.Ala131= 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.Ala155Val Uncertain significance ★ ⚠ same type
BUB3 p.Ala187Gly Uncertain significance ★ ⚠ same type
BUB3 p.Ala239Gly Uncertain significance ★ ⚠ same type
BUB3 p.Ala292Val 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-ala131val (accessed [today's date]).

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