Is AURKAIP1 p.Pro192Ser (c.574C>T) pathogenic?

AURKAIP1 p.Pro192Ser (c.574C>T) is classified Uncertain significance in AURKAIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely pathogenic (0.9253); Ultra-rare (popmax 0.0529%, mid).

How common is AURKAIP1 p.Pro192Ser (c.574C>T) in the general population?

AURKAIP1 p.Pro192Ser (c.574C>T) is ultra-rare (popmax 0.0529%, mid) (gnomAD).

What do computational predictors say about AURKAIP1 p.Pro192Ser (c.574C>T)?

AlphaMissense predicts likely pathogenic (score 0.9253) — an in-silico prediction, not a clinical call.

AURKAIP1 p.Pro192Ser

c.574C>T · rs1304302177 · VCV2366310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9253 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0529%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9253	likely pathogenic · top 5% in AURKAIP1
REVEL	0.582	indeterminate
SaProt	LLR -13.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 952 bp · p 0.0033 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0529% Middle Eastern · 3/5,670 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00767%

Overall 0.000967% 14/1,448,116 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0529%	1,890
African / African-American	0.0107%	9,348
Remaining individualsnot grpmax-eligible	0.00321%	31,163
South Asian	0.0011%	91,032

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: AURKAIP1
Protein: p.Pro192Ser
Coding: c.574C>T
MANE Select: NM_017900
dbSNP: rs1304302177
Type: single nucleotide variant
Location: chr1:1373827 (GRCh38)
Gene constraint: LOEUF 1.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.14 · 81 PDB

Full AURKAIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AIP p.Glu192Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
AIP p.Glu192Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
AIP p.Glu192Val Uncertain significance ★ same residue
AIP p.Glu192= Likely benign ★ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same type
AIP p.Arg304Ter Pathogenic ★★ same type
AIP p.Arg81Ter Pathogenic ★★ same type
AIP p.Cys238Tyr Likely pathogenic ★★ 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/aurkaip1-p-pro192ser (accessed [today's date]).

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