Is AIM2 p.Ter344Glu (c.1030T>G) pathogenic?

AIM2 p.Ter344Glu (c.1030T>G) is classified Conflicting classifications of pathogenicity in AIM2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2020-08-01). Low-frequency (popmax 3.62%, afr); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with AIM2 p.Ter344Glu (c.1030T>G)?

AIM2 p.Ter344Glu (c.1030T>G) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is AIM2 p.Ter344Glu (c.1030T>G) in the general population?

AIM2 p.Ter344Glu (c.1030T>G) is low-frequency (popmax 3.62%, afr) (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

AIM2 p.Ter344Glu

c.1030T>G · rs74689714 · VCV780267

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 3.62%, afr)

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -0.95, phastCons 0.042
Overall
CADD	0.211	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 3.62% African / African-American · 2,705/74,634 alleles

Filtering AF 3.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.46%

Overall 0.197% 3,177/1,612,214 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.62%	28
Middle Eastern	0.264%	379
Ashkenazi Jewishnot grpmax-eligible	0.26%	384
Admixed American	0.241%	415
Remaining individualsnot grpmax-eligible	0.223%	449
South Asian	0.0088%	11,362
European (non-Finnish)	0.00746%	13,401

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.Ter344Glu
Coding: c.1030T>G
MANE Select: NM_004833
dbSNP: rs74689714
Type: single nucleotide variant
Location: chr1:159062694 (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

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

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-ter344glu (accessed [today's date]).

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