Is ARID3A p.Ala487Thr (c.1459G>A) pathogenic?

ARID3A p.Ala487Thr (c.1459G>A) is classified Uncertain significance in ARID3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.0711); Absent from gnomAD v4.1.

How common is ARID3A p.Ala487Thr (c.1459G>A) in the general population?

ARID3A p.Ala487Thr (c.1459G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARID3A p.Ala487Thr (c.1459G>A)?

AlphaMissense predicts likely benign (score 0.0711) — an in-silico prediction, not a clinical call.

ARID3A p.Ala487Thr

c.1459G>A · VCV4642870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0711 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0711	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 0.34, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 7,135 bp · p 0.013 · regional, not allelic
Overall
CADD	22.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARID3A
Protein: p.Ala487Thr
Coding: c.1459G>A
MANE Select: NM_005224
Type: single nucleotide variant
Location: chr19:966832 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.23 · 2 PDB
Residue 487: the rekles domain; the 'important for nuclear localization' region

Full ARID3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARID3A c.950+3G>A Benign ★★ same type
ARID3A p.Ala486= Benign ★★ same type
ARID3A p.Glu447= Benign ★★ same type
ARID3A p.Gly551= Benign ★★ same type
ARID3A p.Ser522= Benign/Likely benign ★★ same type
ARID3A p.Ala171Thr Uncertain significance ★ ⚠ same type
ARID3A p.Ala182Val Uncertain significance ★ ⚠ same type
ARID3A p.Ala209Thr 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/arid3a-p-ala487thr (accessed [today's date]).

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