Is ADAR c.*2A>G pathogenic?

ADAR c.2A>G is classified Likely benign in ADAR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-21). Ultra-rare (popmax 0.01%, amr); Associated with ADAR-related disorder.

What condition is associated with ADAR c.*2A>G?

ADAR c.*2A>G is associated with ADAR-related disorder (ClinVar).

How common is ADAR c.*2A>G in the general population?

ADAR c.*2A>G is ultra-rare (popmax 0.01%, amr) (gnomAD).

ADAR c.*2A>G

rs769951204 · VCV3058649

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

ADAR-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.67	GERP -2.2
Non-coding constraint	Z 1.40	1 kb window · o/e 0.89 · regional · uncalibrated
Overall
CADD	8.686	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,998 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00161% 26/1,610,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.00962%	10,391
African / African-American	0.00134%	74,860
European (non-Finnish)	0.0011%	90,579

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: ADAR
Coding: c.*2A>G
MANE Select: NM_001111
dbSNP: rs769951204
Type: single nucleotide variant
Location: chr1:154584804 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB

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

Disease context

ADAR-related disorder

Similar variants

ADAR p.Arg474Ter Pathogenic ★★ same condition
ADAR p.Arg534Ter Pathogenic ★★ same condition
ADAR p.Asp336Asn Uncertain significance ★★ ⚠ same condition
ADAR p.Gly1050Arg Uncertain significance ★★ ⚠ same condition
ADAR p.Gly215Ser Uncertain significance ★★ ⚠ same condition
ADAR p.Lys495Ter Likely pathogenic ★ same condition
ADAR p.Glu1193Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
ADAR c.42+3A>G Likely 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/adar-c-star-2a-g (accessed [today's date]).

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