Is ADAR p.Arg534Ter (c.1600C>T) pathogenic?

ADAR p.Arg534Ter (c.1600C>T) is classified Pathogenic in ADAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-05). Very rare (popmax 8.47e-05%, nfe); Associated with ADAR-related disorder.

What condition is associated with ADAR p.Arg534Ter (c.1600C>T)?

ADAR p.Arg534Ter (c.1600C>T) is associated with ADAR-related disorder (ClinVar).

How common is ADAR p.Arg534Ter (c.1600C>T) in the general population?

ADAR p.Arg534Ter (c.1600C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ADAR p.Arg534Ter

c.1600C>T · rs1364222107 · VCV2633764

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

ADAR-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 0.47, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,020 alleles

Overall 6.84e-05% 1/1,461,818 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.Arg534Ter
Coding: c.1600C>T
MANE Select: NM_001111
dbSNP: rs1364222107
Type: single nucleotide variant
Location: chr1:154601042 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 534: the drbm 1 domain

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.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
ADAR c.*2A>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-p-arg534ter (accessed [today's date]).

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