Is BUB1B p.Ile242Val (c.724A>G) pathogenic?

BUB1B p.Ile242Val (c.724A>G) is classified Uncertain significance in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-27). AlphaMissense: likely benign (0.067); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ile242Val (c.724A>G)?

BUB1B p.Ile242Val (c.724A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Ile242Val (c.724A>G) in the general population?

BUB1B p.Ile242Val (c.724A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BUB1B p.Ile242Val (c.724A>G)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

BUB1B p.Ile242Val

c.724A>G · rs1249369516 · VCV1757898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -4.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.6	GERP 0.83, phastCons 0.99
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	16.15	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000991% 16/1,614,014 alleles · ultra-rare exomes 14/1,461,782 · genomes 2/152,232 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Finnishnot grpmax-eligible	0.0125%	8,005
East Asian	0.00223%	44,888
European (non-Finnish)	0.000508%	196,662

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.Ile242Val
Coding: c.724A>G
MANE Select: NM_001211
dbSNP: rs1249369516
Type: single nucleotide variant
Location: chr15:40183856 (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.Ile242Thr 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
BUB1B p.Ala173Thr Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala183Thr 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-ile242val (accessed [today's date]).

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