Is ARID2 p.Pro483Ser (c.1447C>T) pathogenic?

ARID2 p.Pro483Ser (c.1447C>T) is classified Uncertain significance in ARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-05). AlphaMissense: likely benign (0.1349); Very rare (popmax 0.0022%, sas); Associated with Coffin-Siris syndrome 6.

What condition is associated with ARID2 p.Pro483Ser (c.1447C>T)?

ARID2 p.Pro483Ser (c.1447C>T) is associated with Coffin-Siris syndrome 6 (ClinVar).

How common is ARID2 p.Pro483Ser (c.1447C>T) in the general population?

ARID2 p.Pro483Ser (c.1447C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ARID2 p.Pro483Ser (c.1447C>T)?

AlphaMissense predicts likely benign (score 0.1349) — an in-silico prediction, not a clinical call.

ARID2 p.Pro483Ser

c.1447C>T · rs374540100 · VCV2439201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1349 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Coffin-Siris syndrome 6

Computational evidence

Protein change
AlphaMissense	0.1349	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.71	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 6.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.0001 · regional, not allelic
Overall
CADD	24.5	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 0.0022% South Asian · 2/91,092 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.00031% 5/1,613,932 alleles · very rare exomes 4/1,461,814 · genomes 1/152,118 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,546
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00134%	74,892
European (non-Finnish)	8.47e-05%	1,180,006

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.Pro483Ser
Coding: c.1447C>T
MANE Select: NM_152641
dbSNP: rs374540100
Type: single nucleotide variant
Location: chr12:45839445 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 483: 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 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARID2 p.Arg1272Ter Pathogenic ★★ same condition
ARID2 p.Arg1754Ter Pathogenic ★★ same condition
ARID2 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same condition
ARID2 p.Gln920Ter Pathogenic ★★ same condition
ARID2 p.Asn302Ser Uncertain significance ★★ ⚠ same condition
ARID2 p.Glu112Ala Uncertain significance ★★ same condition
ARID2 p.Glu1413Gly Uncertain significance ★★ ⚠ same condition
ARID2 p.Ala1434Ser Benign ★★ 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-pro483ser (accessed [today's date]).

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