Is BUB1B p.Arg317fs (c.948_966del19) pathogenic?

BUB1B p.Arg317fs (c.948966del19) is classified Likely pathogenic in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-19). Very rare (popmax 0.000254%, nfe).

How common is BUB1B p.Arg317fs (c.948_966del19) in the general population?

BUB1B p.Arg317fs (c.948_966del19) is very rare (popmax 0.000254%, nfe) (gnomAD).

BUB1B p.Arg317fs

c.948_966del19 · rs1309303130 · VCV2690554

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.75	GERP -1.8, phastCons 0.005
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	GCAGGCCCTTGGAACACAG simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,026 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,020 alleles · very rare exomes 3/1,461,884 · genomes 0/152,136 · joint denominator

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.Arg317fs
Coding: c.948_966del19
MANE Select: NM_001211
dbSNP: rs1309303130
Type: Deletion
Location: chr15:40185347 (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

Similar variants

BUB1B p.Arg317Gly Uncertain significance ★ ⚠ same residue
BUB1B p.Arg317Lys Uncertain significance ★ ⚠ same residue
BUB1B p.Arg317Ser Uncertain significance ★ ⚠ same residue
BUB1B p.Arg317= Likely benign ★ same residue
BUB1B p.Ala957fs Likely pathogenic ★★ same type
BUB1B p.Arg80_Tyr81insTer Pathogenic/Likely pathogenic ★★ same type
BUB1B p.His856fs Pathogenic/Likely pathogenic ★★ same type
BUB1B c.1628+24_1628+32del Likely benign ★★ 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/bub1b-p-arg317fs (accessed [today's date]).

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