Is ADAR p.Arg328Ter (c.982C>T) pathogenic?

ADAR p.Arg328Ter (c.982C>T) is classified Pathogenic in ADAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-27). Very rare (popmax 0.0022%, sas); Associated with dyschromatosis symmetrica hereditaria.

What condition is associated with ADAR p.Arg328Ter (c.982C>T)?

ADAR p.Arg328Ter (c.982C>T) is associated with dyschromatosis symmetrica hereditaria, Aicardi-Goutieres syndrome 6 (ClinVar).

How common is ADAR p.Arg328Ter (c.982C>T) in the general population?

ADAR p.Arg328Ter (c.982C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

How is Dyschromatosis symmetrica hereditaria inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ADAR p.Arg328Ter

c.982C>T · rs1322905273 · VCV1456115

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 0.0022%, sas)

Conditions

dyschromatosis symmetrica hereditaria

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 10	GERP 0.64, phastCons 1
Overall
CADD	38.0	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 0.0022% South Asian · 2/91,080 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000274% 4/1,461,734 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,540
European (non-Finnish)	0.000169%	590,023

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.Arg328Ter
Coding: c.982C>T
MANE Select: NM_001111
dbSNP: rs1322905273
Type: single nucleotide variant
Location: chr1:154601660 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 328: the z-binding 2 domain; an α-helix

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

Disease context

dyschromatosis symmetrica hereditaria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Aicardi-Goutieres syndrome 6

For Dyschromatosis symmetrica hereditaria (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

ADAR p.Arg328Gln Uncertain significance ★★ ⚠ same residue
ADAR c.2885+1G>A Likely pathogenic ★★ same condition
ADAR p.Arg1078Cys Pathogenic ★★ same condition
ADAR p.Arg1096Ter Pathogenic/Likely pathogenic ★★ same condition
ADAR p.Arg360Ter Pathogenic/Likely pathogenic ★★ same condition
ADAR p.Arg474Ter Pathogenic ★★ same condition
ADAR p.Gln559Ter Pathogenic ★★ same condition
ADAR p.Lys1122Gln Likely pathogenic ★★ ⚠ 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-arg328ter (accessed [today's date]).

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