Is AIM2 p.Asp117Tyr (c.349G>T) pathogenic?

AIM2 p.Asp117Tyr (c.349G>T) is classified Uncertain significance in AIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-19). AlphaMissense: likely benign (0.1019); Absent from gnomAD v4.1.

How common is AIM2 p.Asp117Tyr (c.349G>T) in the general population?

AIM2 p.Asp117Tyr (c.349G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIM2 p.Asp117Tyr (c.349G>T)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

AIM2 p.Asp117Tyr

c.349G>T · rs2525254724 · VCV2538669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.55	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 -2.6	GERP -0.014
Regional constraint	o/e 0.87	unconstrained · MANE · 11 kb · p 0.0086 · regional, not allelic
Overall
CADD	0.39	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AIM2
Protein: p.Asp117Tyr
Coding: c.349G>T
MANE Select: NM_004833
dbSNP: rs2525254724
Type: single nucleotide variant
Location: chr1:159068615 (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

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-asp117tyr (accessed [today's date]).

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