Is BUB1B p.Phe340Leu (c.1020C>A) pathogenic?

BUB1B p.Phe340Leu (c.1020C>A) is classified Uncertain significance in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-29). AlphaMissense: likely pathogenic (0.9793); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Phe340Leu (c.1020C>A)?

BUB1B p.Phe340Leu (c.1020C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Phe340Leu (c.1020C>A) in the general population?

BUB1B p.Phe340Leu (c.1020C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BUB1B p.Phe340Leu (c.1020C>A)?

AlphaMissense predicts likely pathogenic (score 0.9793) — an in-silico prediction, not a clinical call.

BUB1B p.Phe340Leu

c.1020C>A · rs2542536308 · VCV3221322

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9793 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9793	likely pathogenic · top 1% in BUB1B
REVEL	0.264	benign-leaning
SaProt	LLR -9.73	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	22.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BUB1B
Protein: p.Phe340Leu
Coding: c.1020C>A
MANE Select: NM_001211
dbSNP: rs2542536308
Type: single nucleotide variant
Location: chr15:40185604 (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.Phe340= Likely benign ★ 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-phe340leu (accessed [today's date]).

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