Is AURKC p.Pro207= (c.621G>A) pathogenic?

AURKC p.Pro207= (c.621G>A) is classified Likely benign in AURKC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-01-13). Low-frequency (popmax 2.06%, afr); Associated with spermatogenic failure 5.

What condition is associated with AURKC p.Pro207= (c.621G>A)?

AURKC p.Pro207= (c.621G>A) is associated with spermatogenic failure 5 (ClinVar).

How common is AURKC p.Pro207= (c.621G>A) in the general population?

AURKC p.Pro207= (c.621G>A) is low-frequency (popmax 2.06%, afr) (gnomAD).

AURKC p.Pro207=

c.621G>A · rs148940837 · VCV330232

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.06%, 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 -2.3	GERP -3.4
Overall
CADD	10.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.06% African / African-American · 1,548/75,012 alleles

Filtering AF 1.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.94%

Overall 0.114% 1,833/1,614,124 alleles · low-frequency exomes 924/1,461,890 · genomes 909/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.06%	48
Admixed American	0.185%	541
Remaining individualsnot grpmax-eligible	0.11%	906
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.00814%	12,292
South Asian	0.00549%	18,216

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.Pro207=
Coding: c.621G>A
MANE Select: NM_001015878
dbSNP: rs148940837
Type: single nucleotide variant
Location: chr19:57234920 (GRCh38)
Gene constraint: LOEUF 0.806 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.25 · 3 PDB
Residue 207: the protein kinase domain

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.Pro207Leu 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
AURKC c.*38G>A 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-pro207 (accessed [today's date]).

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