Is AIM2 p.Thr343fs (c.1027del) pathogenic?

AIM2 p.Thr343fs (c.1027del) is classified Benign in AIM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-02-12). Rare (popmax 0.82%, mid); Associated with AIM2-related disorder.

What condition is associated with AIM2 p.Thr343fs (c.1027del)?

AIM2 p.Thr343fs (c.1027del) is associated with AIM2-related disorder (ClinVar).

How common is AIM2 p.Thr343fs (c.1027del) in the general population?

AIM2 p.Thr343fs (c.1027del) is rare (popmax 0.82%, mid) (gnomAD).

AIM2 p.Thr343fs

c.1027del · rs531843702 · VCV3041346

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.82%, mid)

Conditions

AIM2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.69	GERP -1, phastCons 0.001
Overall
CADD	17.97	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.82% Middle Eastern · 44/5,368 alleles

Filtering AF 0.627% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.56%

Overall 0.443% 6,156/1,390,226 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.82%	122
Ashkenazi Jewishnot grpmax-eligible	0.591%	169
European (non-Finnish)	0.497%	201
Remaining individualsnot grpmax-eligible	0.436%	229
Admixed American	0.428%	234
Finnishnot grpmax-eligible	0.363%	275
South Asian	0.211%	473
African / African-American	0.136%	735
East Asian	0.0313%	3,194

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.Thr343fs
Coding: c.1027del
MANE Select: NM_004833
dbSNP: rs531843702
Type: Deletion
Location: chr1:159062697 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.18 · 6 PDB

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

Disease context

AIM2-related disorder

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-thr343fs (accessed [today's date]).

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