Is ARID2 p.Pro513Ala (c.1537C>G) pathogenic?

ARID2 p.Pro513Ala (c.1537C>G) is classified Uncertain significance in ARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0676); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with ARID2 p.Pro513Ala (c.1537C>G)?

ARID2 p.Pro513Ala (c.1537C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARID2 p.Pro513Ala (c.1537C>G) in the general population?

ARID2 p.Pro513Ala (c.1537C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ARID2 p.Pro513Ala (c.1537C>G)?

AlphaMissense predicts likely benign (score 0.0676) — an in-silico prediction, not a clinical call.

ARID2 p.Pro513Ala

c.1537C>G · rs1387137586 · VCV2490214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0676	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.74	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 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.0001 · regional, not allelic
Overall
CADD	22.1	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 0.00167% Admixed American · 1/59,980 alleles

Overall 6.85e-05% 1/1,460,910 alleles · very rare

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.Pro513Ala
Coding: c.1537C>G
MANE Select: NM_152641
dbSNP: rs1387137586
Type: single nucleotide variant
Location: chr12:45846894 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 513: 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-pro513ala (accessed [today's date]).

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