Is AURKC p.Pro4= (c.12C>G) pathogenic?

AURKC p.Pro4= (c.12C>G) is classified Uncertain significance in AURKC (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.733%, afr); Associated with spermatogenic failure 5.

What condition is associated with AURKC p.Pro4= (c.12C>G)?

AURKC p.Pro4= (c.12C>G) is associated with spermatogenic failure 5 (ClinVar).

How common is AURKC p.Pro4= (c.12C>G) in the general population?

AURKC p.Pro4= (c.12C>G) is rare (popmax 0.733%, afr) (gnomAD).

AURKC p.Pro4=

c.12C>G · rs73633650 · VCV893061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.733%, afr)

Conditions

spermatogenic failure 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -1.3
Overall
CADD	0.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.733% African / African-American · 536/73,156 alleles

Filtering AF 0.681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.661%

Overall 0.0418% 649/1,552,262 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.733%	136
Admixed American	0.0606%	1,650
Middle Eastern	0.0501%	1,997
Remaining individualsnot grpmax-eligible	0.0399%	2,506
South Asian	0.0333%	3,003
European (non-Finnish)	0.00235%	42,492

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.Pro4=
Coding: c.12C>G
MANE Select: NM_001015878
dbSNP: rs73633650
Type: single nucleotide variant
Location: chr19:57231260 (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

spermatogenic failure 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Male infertility with teratozoospermia due to single gene mutation (Orphanet):

Onset: Adolescent, Adult

Similar variants

AURKC p.Pro4Arg Uncertain significance ★ ⚠ same residue
AURKC p.Pro4Leu Uncertain significance ★ ⚠ same residue
AURKC p.Tyr248Ter Pathogenic ★★ same condition
AURKC c.436-4A>G Uncertain significance ★★ same condition
AURKC p.Ile225= Uncertain significance ★★ same condition
AURKC p.Val254= Uncertain significance ★★ same condition
AURKC c.-128C>T Benign ★★ same condition
AURKC c.-145G>C Benign ★★ 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-pro4 (accessed [today's date]).

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