Is AURKB p.Arg309Ser (c.927G>C) pathogenic?

AURKB p.Arg309Ser (c.927G>C) is classified Uncertain significance in AURKB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely pathogenic (0.6163); Very rare (popmax 0.00135%, afr).

How common is AURKB p.Arg309Ser (c.927G>C) in the general population?

AURKB p.Arg309Ser (c.927G>C) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about AURKB p.Arg309Ser (c.927G>C)?

AlphaMissense predicts likely pathogenic (score 0.6163) — an in-silico prediction, not a clinical call.

AURKB p.Arg309Ser

c.927G>C · rs1567567792 · VCV3132352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6163 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6163	likely pathogenic
REVEL	0.059	moderately benign-leaning
SaProt	LLR -12.49	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -4.1, phastCons 0.06
Regional constraint	o/e 0.87	unconstrained · MANE · 1,966 bp · p 0.034 · regional, not allelic
Overall
CADD	19.76	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 0.00135% African / African-American · 1/74,202 alleles

Overall 0.000187% 3/1,608,348 alleles · very rare exomes 2/1,456,430 · genomes 1/151,918 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,198
African / African-Americangrpmax	0.00135%	74,202
European (non-Finnish)	8.48e-05%	1,178,582

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AURKB
Protein: p.Arg309Ser
Coding: c.927G>C
MANE Select: NM_004217
dbSNP: rs1567567792
Type: single nucleotide variant
Location: chr17:8204979 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.71 · 1 PDB
Residue 309: the protein kinase domain

Full AURKB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AURKB p.Gly212Arg Benign/Likely benign ★★ same type
AURKB p.Ala185Ser Uncertain significance ★ ⚠ same type
AURKB p.Arg159Cys Uncertain significance ★ ⚠ same type
AURKB p.Arg176Leu Uncertain significance ★ same type
AURKB p.Arg248Cys Uncertain significance ★ ⚠ same type
AURKB p.Arg44Cys Uncertain significance ★ ⚠ same type
AURKB p.Arg95Gly Uncertain significance ★ ⚠ same type
AURKB p.Asn279Lys 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/aurkb-p-arg309ser (accessed [today's date]).

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