Is AIM2 p.Arg67His (c.200G>A) pathogenic?

AIM2 p.Arg67His (c.200G>A) is classified Uncertain significance in AIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-10). AlphaMissense: likely benign (0.0725); Very rare (popmax 0.00797%, nfe).

How common is AIM2 p.Arg67His (c.200G>A) in the general population?

AIM2 p.Arg67His (c.200G>A) is very rare (popmax 0.00797%, nfe) (gnomAD).

What do computational predictors say about AIM2 p.Arg67His (c.200G>A)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

AIM2 p.Arg67His

c.200G>A · VCV3846335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00797%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -13	GERP -2.2
Regional constraint	o/e 0.87	unconstrained · MANE · 11 kb · p 0.0086 · regional, not allelic
Overall
CADD	0.002	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 0.00797% European (non-Finnish) · 94/1,180,040 alleles

Filtering AF 0.00664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00616%

Overall 0.00589% 95/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00797%	12,554
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: AIM2
Protein: p.Arg67His
Coding: c.200G>A
MANE Select: NM_004833
Type: single nucleotide variant
Location: chr1:159073300 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.18 · 6 PDB
Residue 67: the pyrin domain; an α-helix

Full AIM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AIM2 c.396+6A>T Benign ★★ same type
AIM2 p.Glu83= Benign ★★ same type
AIM2 p.Pro250= Benign ★★ same type
AIM2 p.Ala112Ser Uncertain significance ★ ⚠ same type
AIM2 p.Ala230Val Uncertain significance ★ ⚠ same type
AIM2 p.Arg115Gly Uncertain significance ★ ⚠ same type
AIM2 p.Arg205Thr Uncertain significance ★ ⚠ same type
AIM2 p.Arg211Ile 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/aim2-p-arg67his (accessed [today's date]).

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