Is ARID2 p.Val1385Ile (c.4153G>A) pathogenic?

ARID2 p.Val1385Ile (c.4153G>A) is classified Uncertain significance in ARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.0883); Very rare (popmax 0.0072%, nfe).

How common is ARID2 p.Val1385Ile (c.4153G>A) in the general population?

ARID2 p.Val1385Ile (c.4153G>A) is very rare (popmax 0.0072%, nfe) (gnomAD).

What do computational predictors say about ARID2 p.Val1385Ile (c.4153G>A)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

ARID2 p.Val1385Ile

c.4153G>A · rs781522138 · VCV2637735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0072%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -6.42	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 9.9	GERP 2.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,024 bp · p 0.35 · regional, not allelic
Overall
CADD	22.7	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 0.0072% European (non-Finnish) · 85/1,180,018 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00533% 86/1,614,030 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0072%	13,883
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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.Val1385Ile
Coding: c.4153G>A
MANE Select: NM_152641
dbSNP: rs781522138
Type: single nucleotide variant
Location: chr12:45852276 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 1385: a UniProt-annotated variant site (in css6)

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-val1385ile (accessed [today's date]).

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