Is AURKC p.Ser32Ile (c.95G>T) pathogenic?

AURKC p.Ser32Ile (c.95G>T) is classified Uncertain significance in AURKC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.1097); Ultra-rare (popmax 0.0284%, amr); Associated with Inborn genetic diseases.

What condition is associated with AURKC p.Ser32Ile (c.95G>T)?

AURKC p.Ser32Ile (c.95G>T) is associated with Inborn genetic diseases (ClinVar).

How common is AURKC p.Ser32Ile (c.95G>T) in the general population?

AURKC p.Ser32Ile (c.95G>T) is ultra-rare (popmax 0.0284%, amr) (gnomAD).

What do computational predictors say about AURKC p.Ser32Ile (c.95G>T)?

AlphaMissense predicts likely benign (score 0.1097) — an in-silico prediction, not a clinical call.

AURKC p.Ser32Ile

c.95G>T · rs748307098 · VCV2514915

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1097 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0284%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1097	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -8.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7	GERP -1.9
Regional constraint	o/e 0.87	unconstrained · MANE · 4,165 bp · p 0.0089 · regional, not allelic
Overall
CADD	0.034	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 0.0284% Admixed American · 17/59,940 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0148%

Overall 0.00459% 74/1,613,770 alleles · ultra-rare exomes 55/1,461,844 · genomes 19/151,926 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0284%	3,526
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00441%	22,692

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: AURKC
Protein: p.Ser32Ile
Coding: c.95G>T
MANE Select: NM_001015878
dbSNP: rs748307098
Type: single nucleotide variant
Location: chr19:57231778 (GRCh38)
Gene constraint: LOEUF 0.806 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.25 · 3 PDB
Residue 32: the 'disordered' region

Full AURKC 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

AURKC p.Ser32Arg Uncertain significance ★ ⚠ same residue
AURKC p.Ser32fs Likely pathogenic ★ same residue
AURKC p.Ala113Val Uncertain significance ★ ⚠ same condition
AURKC p.Arg114His Uncertain significance ★ ⚠ same condition
AURKC p.Arg115Trp Uncertain significance ★ ⚠ same condition
AURKC p.Arg142Cys Uncertain significance ★ ⚠ same condition
AURKC p.Arg250His Uncertain significance ★ ⚠ same condition
AURKC p.Arg299Lys 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/aurkc-p-ser32ile (accessed [today's date]).

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