Is AURKA p.Ser391Pro (c.1171T>C) pathogenic?

AURKA p.Ser391Pro (c.1171T>C) is classified Uncertain significance in AURKA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely benign (0.0515); Absent from gnomAD v4.1.

How common is AURKA p.Ser391Pro (c.1171T>C) in the general population?

AURKA p.Ser391Pro (c.1171T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AURKA p.Ser391Pro (c.1171T>C)?

AlphaMissense predicts likely benign (score 0.0515) — an in-silico prediction, not a clinical call.

AURKA p.Ser391Pro

c.1171T>C · VCV3467123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0515 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0515	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -1.72	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 -0.13	GERP -5
Regional constraint	o/e 0.70	unconstrained · MANE · 18 kb · p 7.1e-11 · regional, not allelic
Overall
CADD	4.107	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AURKA
Protein: p.Ser391Pro
Coding: c.1171T>C
MANE Select: NM_198437
Type: single nucleotide variant
Location: chr20:56370199 (GRCh38)
Gene constraint: LOEUF 0.528 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 76.07 · 202 PDB

Full AURKA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AURKA p.Asn7= Benign ★★ same type
AURKA p.Phe31Ile Benign ★★ same type
AURKA c.-5-7T>G Uncertain significance ★ same type
AURKA p.Ala105Val Uncertain significance ★ ⚠ same type
AURKA p.Arg251Thr Uncertain significance ★ ⚠ same type
AURKA p.Arg362Ile Uncertain significance ★ ⚠ same type
AURKA p.Arg3Leu Uncertain significance ★ ⚠ same type
AURKA p.Asn367Asp Uncertain significance ★ ⚠ same type

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/aurka-p-ser391pro (accessed [today's date]).

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