Is AZIN2 p.Arg412Trp (c.1234C>T) pathogenic?

AZIN2 p.Arg412Trp (c.1234C>T) is classified Uncertain significance in AZIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-26). AlphaMissense: likely benign (0.1471); Very rare (popmax 0.00237%, eas).

How common is AZIN2 p.Arg412Trp (c.1234C>T) in the general population?

AZIN2 p.Arg412Trp (c.1234C>T) is very rare (popmax 0.00237%, eas) (gnomAD).

What do computational predictors say about AZIN2 p.Arg412Trp (c.1234C>T)?

AlphaMissense predicts likely benign (score 0.1471) — an in-silico prediction, not a clinical call.

AZIN2 p.Arg412Trp

c.1234C>T · rs750759779 · VCV2402640

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1471 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1471	likely benign
REVEL	0.335	indeterminate
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -2.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,228 bp · p 0.24 · regional, not allelic
Overall
CADD	27.8	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 0.00237% East Asian · 1/42,190 alleles

Filtering AF 0.000258% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000664% 10/1,507,014 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00237%	42,190
Admixed American	0.00236%	42,320
African / African-American	0.00142%	70,640
European (non-Finnish)	0.000619%	161,498

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.Arg412Trp
Coding: c.1234C>T
MANE Select: NM_052998
dbSNP: rs750759779
Type: single nucleotide variant
Location: chr1:33118106 (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.Arg419Leu Uncertain significance ★ ⚠ same type
AZIN2 p.Arg64Pro 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-arg412trp (accessed [today's date]).

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