Is AZIN2 p.Pro397Arg (c.1190C>G) pathogenic?

AZIN2 p.Pro397Arg (c.1190C>G) is classified Uncertain significance in AZIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0727); Very rare (popmax 0.00223%, amr).

How common is AZIN2 p.Pro397Arg (c.1190C>G) in the general population?

AZIN2 p.Pro397Arg (c.1190C>G) is very rare (popmax 0.00223%, amr) (gnomAD).

What do computational predictors say about AZIN2 p.Pro397Arg (c.1190C>G)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

AZIN2 p.Pro397Arg

c.1190C>G · rs1019319311 · VCV3132511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.34	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 1.1	GERP -1.8, phastCons 0.51
Regional constraint	o/e 0.90	unconstrained · MANE · 2,228 bp · p 0.24 · regional, not allelic
Overall
CADD	2.064	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

Grpmax group 0.00223% Admixed American · 1/44,858 alleles

Overall 7.27e-05% 1/1,375,046 alleles · very rare

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: AZIN2
Protein: p.Pro397Arg
Coding: c.1190C>G
MANE Select: NM_052998
dbSNP: rs1019319311
Type: single nucleotide variant
Location: chr1:33118062 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.94

Full AZIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AZIN2 p.His188Asn Benign ★★ same type
TRIM62 p.Glu234= Benign ★★ same type
TRIM62 p.Val473Ile Benign ★★ same type
AZIN2 p.Ala112Thr Uncertain significance ★ ⚠ same type
AZIN2 p.Arg217Gln Uncertain significance ★ ⚠ same type
AZIN2 p.Arg217Trp Uncertain significance ★ ⚠ same type
AZIN2 p.Arg412Trp Uncertain significance ★ ⚠ same type
AZIN2 p.Arg419Leu 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/azin2-p-pro397arg (accessed [today's date]).

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