Is ARID2 p.Arg558His (c.1673G>A) pathogenic?

ARID2 p.Arg558His (c.1673G>A) is classified Uncertain significance in ARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-27). AlphaMissense: likely pathogenic (0.6512); Very rare (popmax 0.00167%, amr).

How common is ARID2 p.Arg558His (c.1673G>A) in the general population?

ARID2 p.Arg558His (c.1673G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ARID2 p.Arg558His (c.1673G>A)?

AlphaMissense predicts likely pathogenic (score 0.6512) — an in-silico prediction, not a clinical call.

ARID2 p.Arg558His

c.1673G>A · rs1331723696 · VCV3013940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6512 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6512	likely pathogenic
REVEL	0.689	pathogenic-leaning
SaProt	LLR -2.93	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.0001 · regional, not allelic
Overall
CADD	32.0	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 0.00167% Admixed American · 1/59,942 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,612,422 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,942
Remaining individualsnot grpmax-eligible	0.0016%	62,402
African / African-American	0.00134%	74,850
European (non-Finnish)	0.000509%	196,508

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.Arg558His
Coding: c.1673G>A
MANE Select: NM_152641
dbSNP: rs1331723696
Type: single nucleotide variant
Location: chr12:45848928 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 558: a DNA-binding region; a UniProt-annotated variant site (in css6)

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

Similar variants

ARID2 p.Arg558Pro Uncertain significance ★ ⚠ same residue
ARID2 p.Arg1272Ter Pathogenic ★★ same type
ARID2 p.Arg1677Ter Pathogenic/Likely pathogenic ★★ same type
ARID2 p.Arg1754Ter Pathogenic ★★ same type
ARID2 p.Arg1769Ter Pathogenic ★★ same type
ARID2 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same type
ARID2 p.Gln920Ter Pathogenic ★★ same type
ARID2 p.Ala1335Glu 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/arid2-p-arg558his (accessed [today's date]).

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