Is ARID2 p.Ser472Arg (c.1414A>C) pathogenic?

ARID2 p.Ser472Arg (c.1414A>C) is classified Likely benign in ARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). AlphaMissense: ambiguous (0.4965); Ultra-rare (popmax 0.0108%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARID2 p.Ser472Arg (c.1414A>C)?

ARID2 p.Ser472Arg (c.1414A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ARID2 p.Ser472Arg (c.1414A>C) in the general population?

ARID2 p.Ser472Arg (c.1414A>C) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

What do computational predictors say about ARID2 p.Ser472Arg (c.1414A>C)?

AlphaMissense predicts ambiguous (score 0.4965) — an in-silico prediction, not a clinical call.

ARID2 p.Ser472Arg

c.1414A>C · rs748902977 · VCV2463494

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4965 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4965	ambiguous
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.41	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.0001 · regional, not allelic
Overall
CADD	23.7	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 0.0108% European (non-Finnish) · 127/1,180,012 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00863%

Overall 0.00812% 131/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0108%	9,291
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00133%	74,934

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.Ser472Arg
Coding: c.1414A>C
MANE Select: NM_152641
dbSNP: rs748902977
Type: single nucleotide variant
Location: chr12:45839412 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 472: a UniProt-annotated variant site (in css6)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARID2 p.Arg1769Ter Pathogenic ★★ same condition
ARID2 p.Ala1335Glu Uncertain significance ★★ ⚠ same condition
ARID2 p.Asn1280Asp Uncertain significance ★★ ⚠ same condition
ARID2 p.Asp1400Gly Uncertain significance ★★ ⚠ same condition
ARID2 p.Gln752Lys Uncertain significance ★★ ⚠ same condition
ARID2 p.Ile943Phe Uncertain significance ★★ ⚠ same condition
ARID2 p.Ser990Leu Uncertain significance ★★ ⚠ same condition
ARID2 p.Thr1474Ala Uncertain significance ★★ ⚠ same condition

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-ser472arg (accessed [today's date]).

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