Is BUB1B p.Phe410= (c.1230C>T) pathogenic?

BUB1B p.Phe410= (c.1230C>T) is classified Benign/Likely benign in BUB1B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Rare (popmax 0.265%, afr); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Phe410= (c.1230C>T)?

BUB1B p.Phe410= (c.1230C>T) is associated with Inborn genetic diseases, colorectal cancer, premature chromatid separation trait (ClinVar).

How common is BUB1B p.Phe410= (c.1230C>T) in the general population?

BUB1B p.Phe410= (c.1230C>T) is rare (popmax 0.265%, afr) (gnomAD).

BUB1B p.Phe410=

c.1230C>T · rs61733369 · VCV412525

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.265%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -1.8, phastCons 1
Overall
CADD	9.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.265% African / African-American · 199/75,018 alleles

Filtering AF 0.235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.223%

Overall 0.0147% 238/1,614,002 alleles · rare exomes 103/1,461,760 · genomes 135/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.265%	377
Middle Eastern	0.033%	3,031
Admixed American	0.0267%	3,750
Remaining individualsnot grpmax-eligible	0.016%	6,251
South Asian	0.0011%	91,072
European (non-Finnish)	0.000848%	117,992

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.Phe410=
Coding: c.1230C>T
MANE Select: NM_001211
dbSNP: rs61733369
Type: single nucleotide variant
Location: chr15:40196716 (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

Also linked: colorectal cancer premature chromatid separation trait mosaic variegated aneuploidy syndrome 1

Similar variants

BUB1B p.Phe410Leu Uncertain significance ★ ⚠ same residue
BUB1B p.Arg114Ter Pathogenic ★★ same condition
BUB1B p.Arg120Ter Pathogenic ★★ same condition
BUB1B p.Arg194Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Arg199Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Arg67Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Gln267Ter Pathogenic ★★ same condition
BUB1B p.Leu737Ter Pathogenic/Likely pathogenic ★★ 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-phe410 (accessed [today's date]).

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