Is AURKC p.Pro124Ser (c.370C>T) pathogenic?

AURKC p.Pro124Ser (c.370C>T) is classified Uncertain significance in AURKC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: ambiguous (0.5122); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with AURKC p.Pro124Ser (c.370C>T)?

AURKC p.Pro124Ser (c.370C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AURKC p.Pro124Ser (c.370C>T) in the general population?

AURKC p.Pro124Ser (c.370C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about AURKC p.Pro124Ser (c.370C>T)?

AlphaMissense predicts ambiguous (score 0.5122) — an in-silico prediction, not a clinical call.

AURKC p.Pro124Ser

c.370C>T · rs762160840 · VCV2548750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5122	ambiguous
REVEL	0.203	benign-leaning
SaProt	LLR -9.13	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,165 bp · p 0.0089 · regional, not allelic
Overall
CADD	23.1	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 0.00446% East Asian · 2/44,866 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000434% 7/1,614,074 alleles · very rare exomes 7/1,461,874 · genomes 0/152,200 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,433
European (non-Finnish)	0.000424%	236,005

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.Pro124Ser
Coding: c.370C>T
MANE Select: NM_001015878
dbSNP: rs762160840
Type: single nucleotide variant
Location: chr19:57232615 (GRCh38)
Gene constraint: LOEUF 0.806 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.25 · 3 PDB
Residue 124: the protein kinase domain

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.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
AURKC p.Arg5Gly Uncertain significance ★ ⚠ same condition
AURKC p.Asn24Lys 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-pro124ser (accessed [today's date]).

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