Is AURKC p.Pro4Leu (c.11C>T) pathogenic?

AURKC p.Pro4Leu (c.11C>T) is classified Uncertain significance in AURKC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.162); Very rare (popmax 0.00476%, sas); Associated with Inborn genetic diseases.

What condition is associated with AURKC p.Pro4Leu (c.11C>T)?

AURKC p.Pro4Leu (c.11C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AURKC p.Pro4Leu (c.11C>T) in the general population?

AURKC p.Pro4Leu (c.11C>T) is very rare (popmax 0.00476%, sas) (gnomAD).

What do computational predictors say about AURKC p.Pro4Leu (c.11C>T)?

AlphaMissense predicts likely benign (score 0.162) — an in-silico prediction, not a clinical call.

AURKC p.Pro4Leu

c.11C>T · rs553335951 · VCV3132354

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00476%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.162	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -7.08	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 -0.93	GERP -1.3
Regional constraint	o/e 0.87	unconstrained · MANE · 4,165 bp · p 0.0089 · regional, not allelic
Overall
CADD	6.709	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 0.00476% South Asian · 4/84,080 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000948%

Overall 0.000838% 13/1,552,170 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00476%	21,020
Admixed American	0.00391%	25,567
Remaining individualsnot grpmax-eligible	0.00166%	60,140
European (non-Finnish)	0.000523%	191,206

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.Pro4Leu
Coding: c.11C>T
MANE Select: NM_001015878
dbSNP: rs553335951
Type: single nucleotide variant
Location: chr19:57231259 (GRCh38)
Gene constraint: LOEUF 0.806 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.25 · 3 PDB
Residue 4: 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.Pro4Arg Uncertain significance ★ ⚠ same residue
AURKC p.Pro4= Uncertain significance ★ 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-pro4leu (accessed [today's date]).

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