Is AIM2 p.Arg214Gln (c.641G>A) pathogenic?

AIM2 p.Arg214Gln (c.641G>A) is classified Likely benign in AIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely benign (0.0838); Very rare (popmax 0.00167%, amr).

How common is AIM2 p.Arg214Gln (c.641G>A) in the general population?

AIM2 p.Arg214Gln (c.641G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AIM2 p.Arg214Gln (c.641G>A)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

AIM2 p.Arg214Gln

c.641G>A · VCV4259508

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.11	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	GERP -2.6
Regional constraint	o/e 0.87	unconstrained · MANE · 11 kb · p 0.0086 · regional, not allelic
Overall
CADD	1.578	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.0013% 21/1,613,994 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed Americangrpmax	0.00167%	59,990
Finnishnot grpmax-eligible	0.00156%	64,014
European (non-Finnish)	0.00127%	78,668
South Asian	0.0011%	91,084

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg214Gln
Coding: c.641G>A
MANE Select: NM_004833
Type: single nucleotide variant
Location: chr1:159066085 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.18 · 6 PDB
Residue 214: the hin-200 domain; a β-strand

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

Similar variants

AIM2 p.Arg214Trp Likely benign ★ same residue
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

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-arg214gln (accessed [today's date]).

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