Is ARID2 p.Ile822= (c.2466C>T) pathogenic?

ARID2 p.Ile822= (c.2466C>T) is classified Likely benign in ARID2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0933%, amr).

How common is ARID2 p.Ile822= (c.2466C>T) in the general population?

ARID2 p.Ile822= (c.2466C>T) is ultra-rare (popmax 0.0933%, amr) (gnomAD).

ARID2 p.Ile822=

c.2466C>T · rs141401951 · VCV784298

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0933%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 2.7, phastCons 1
Overall
CADD	9.596	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0933% Admixed American · 56/59,990 alleles

Filtering AF 0.0737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0667%

Overall 0.0205% 331/1,613,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.497%	201
Admixed Americangrpmax	0.0933%	1,071
Remaining individualsnot grpmax-eligible	0.0688%	1,453
Middle Eastern	0.0657%	1,521
African / African-American	0.00667%	14,984
European (non-Finnish)	0.00602%	16,620
South Asian	0.00439%	22,769
Finnishnot grpmax-eligible	0.00156%	64,008

Ashkenazi Jewish 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: ARID2
Protein: p.Ile822=
Coding: c.2466C>T
MANE Select: NM_152641
dbSNP: rs141401951
Type: single nucleotide variant
Location: chr12:45850589 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 822: a UniProt-annotated variant site (in css6); the 'disordered' region

Full ARID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARID2 p.Arg1272Ter Pathogenic ★★ same type
ARID2 p.Arg1677Ter Pathogenic/Likely pathogenic ★★ same type
ARID2 p.Arg1754Ter Pathogenic ★★ same type
ARID2 p.Arg1769Ter Pathogenic ★★ same type
ARID2 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same type
ARID2 p.Gln920Ter Pathogenic ★★ same type
ARID2 p.Ala1335Glu Uncertain significance ★★ ⚠ same type
ARID2 p.Arg1679Gln 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/arid2-p-ile822 (accessed [today's date]).

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