Is ARID2 p.Ile608Val (c.1822A>G) pathogenic?

ARID2 p.Ile608Val (c.1822A>G) is classified Uncertain significance in ARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely benign (0.0677); Very rare (popmax 0.00329%, sas); Associated with Coffin-Siris syndrome 1.

What condition is associated with ARID2 p.Ile608Val (c.1822A>G)?

ARID2 p.Ile608Val (c.1822A>G) is associated with Coffin-Siris syndrome 1 (ClinVar).

How common is ARID2 p.Ile608Val (c.1822A>G) in the general population?

ARID2 p.Ile608Val (c.1822A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ARID2 p.Ile608Val (c.1822A>G)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

ARID2 p.Ile608Val

c.1822A>G · VCV3731487

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Coffin-Siris syndrome 1

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -4.16	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 3.6	GERP -0.97, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.0001 · regional, not allelic
Overall
CADD	14.23	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 0.00329% South Asian · 3/91,068 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000248% 4/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,356
Remaining individualsnot grpmax-eligible	0.0016%	62,498

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.Ile608Val
Coding: c.1822A>G
MANE Select: NM_152641
Type: single nucleotide variant
Location: chr12:45849686 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 608: a UniProt-annotated variant site (in css6)

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

Disease context

Coffin-Siris syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ile608val (accessed [today's date]).

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