Is AURKC p.Ser32fs (c.94_101del) pathogenic?

AURKC p.Ser32fs (c.94101del) is classified Likely pathogenic in AURKC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-30). Ultra-rare (popmax 0.0825%, mid); Associated with spermatogenic failure 5.

What condition is associated with AURKC p.Ser32fs (c.94_101del)?

AURKC p.Ser32fs (c.94_101del) is associated with spermatogenic failure 5 (ClinVar).

How common is AURKC p.Ser32fs (c.94_101del) in the general population?

AURKC p.Ser32fs (c.94_101del) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

AURKC p.Ser32fs

c.94_101del · rs749123022 · VCV4850651

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Conditions

spermatogenic failure 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.3	GERP -1.2
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	LTR33 ltr, simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,060 alleles

Filtering AF 0.0466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0421%

Overall 0.0205% 331/1,613,434 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
South Asian	0.0593%	1,686
East Asian	0.0357%	2,803
Remaining individualsnot grpmax-eligible	0.0304%	3,289
European (non-Finnish)	0.0184%	5,437
African / African-American	0.0174%	5,748
Admixed American	0.00835%	11,980
Finnishnot grpmax-eligible	0.00313%	31,980

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.Ser32fs
Coding: c.94_101del
MANE Select: NM_001015878
dbSNP: rs749123022
Type: Microsatellite
Location: chr19:57231760 (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

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.Met35fs Conflicting classifications of pathogenicity ★ same condition
AURKC p.Ser32Arg Uncertain significance ★ ⚠ same residue
AURKC p.Ser32Ile Uncertain significance ★ ⚠ same residue
AURKC p.Leu49fs Pathogenic/Likely pathogenic ★★ same condition
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

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-ser32fs (accessed [today's date]).

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