Is ADAR p.Arg74Gly (c.220A>G) pathogenic?

ADAR p.Arg74Gly (c.220A>G) is classified Uncertain significance in ADAR (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-01). AlphaMissense: likely benign (0.0964); Very rare (popmax 0.00167%, amr).

How common is ADAR p.Arg74Gly (c.220A>G) in the general population?

ADAR p.Arg74Gly (c.220A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ADAR p.Arg74Gly (c.220A>G)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

ADAR p.Arg74Gly

c.220A>G · rs1571112467 · VCV806226

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -5.96	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 -0.39	GERP -1.6
Regional constraint	o/e 0.96	unconstrained · MANE · 6,556 bp · p 0.34 · regional, not allelic
Overall
CADD	13.49	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 · 1/59,812 alleles

Overall 6.87e-05% 1/1,456,470 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: ADAR
Protein: p.Arg74Gly
Coding: c.220A>G
MANE Select: NM_001111
dbSNP: rs1571112467
Type: single nucleotide variant
Location: chr1:154602422 (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

Similar variants

ADAR p.Arg74= Likely benign ★★ same residue
ADAR p.Arg74Lys Uncertain significance ★ ⚠ same residue
ADAR c.2885+1G>A Likely pathogenic ★★ same type
ADAR p.Arg1078Cys Pathogenic ★★ same type
ADAR p.Arg1096Ter Pathogenic/Likely pathogenic ★★ same type
ADAR p.Arg328Ter Pathogenic ★★ same type
ADAR p.Arg360Ter Pathogenic/Likely pathogenic ★★ same type
ADAR p.Arg474Ter Pathogenic ★★ 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/adar-p-arg74gly (accessed [today's date]).

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