Is ARID3A p.Phe482Ser (c.1445T>C) pathogenic?

ARID3A p.Phe482Ser (c.1445T>C) is classified Uncertain significance in ARID3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.8703); Very rare (popmax 0.005%, amr).

How common is ARID3A p.Phe482Ser (c.1445T>C) in the general population?

ARID3A p.Phe482Ser (c.1445T>C) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ARID3A p.Phe482Ser (c.1445T>C)?

AlphaMissense predicts likely pathogenic (score 0.8703) — an in-silico prediction, not a clinical call.

ARID3A p.Phe482Ser

c.1445T>C · VCV4642869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8703	likely pathogenic
REVEL	0.145	moderately benign-leaning
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 7,135 bp · p 0.013 · regional, not allelic
Overall
CADD	26.9	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 0.005% Admixed American · 3/60,014 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,613,454 alleles · very rare exomes 3/1,461,140 · genomes 0/152,314 · joint denominator

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: ARID3A
Protein: p.Phe482Ser
Coding: c.1445T>C
MANE Select: NM_005224
Type: single nucleotide variant
Location: chr19:966818 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.23 · 2 PDB
Residue 482: 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-phe482ser (accessed [today's date]).

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