Is AIM2 p.Asn55Asp (c.163A>G) pathogenic?

AIM2 p.Asn55Asp (c.163A>G) is classified Uncertain significance in AIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: likely benign (0.1943); Very rare (popmax 0.00212%, nfe).

How common is AIM2 p.Asn55Asp (c.163A>G) in the general population?

AIM2 p.Asn55Asp (c.163A>G) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about AIM2 p.Asn55Asp (c.163A>G)?

AlphaMissense predicts likely benign (score 0.1943) — an in-silico prediction, not a clinical call.

AIM2 p.Asn55Asp

c.163A>G · rs1388611876 · VCV3102792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1943	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -9.05	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 0.49	GERP 1.3
Regional constraint	o/e 0.87	unconstrained · MANE · 11 kb · p 0.0086 · regional, not allelic
Overall
CADD	13.65	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 0.00212% European (non-Finnish) · 25/1,180,044 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00161% 26/1,614,094 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,202
African / African-American	0.00133%	74,938

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.Asn55Asp
Coding: c.163A>G
MANE Select: NM_004833
dbSNP: rs1388611876
Type: single nucleotide variant
Location: chr1:159073337 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.18 · 6 PDB
Residue 55: 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-asn55asp (accessed [today's date]).

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