Is ADAR p.Cys976del (c.2926_2928del) pathogenic?

ADAR p.Cys976del (c.29262928del) is classified Uncertain significance in ADAR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-27). Absent from gnomAD; Associated with Aicardi-Goutieres syndrome 6.

What condition is associated with ADAR p.Cys976del (c.2926_2928del)?

ADAR p.Cys976del (c.2926_2928del) is associated with Aicardi-Goutieres syndrome 6, dyschromatosis symmetrica hereditaria (ClinVar).

How common is ADAR p.Cys976del (c.2926_2928del) in the general population?

ADAR p.Cys976del (c.2926_2928del) is absent from gnomAD (gnomAD).

How is Aicardi-Goutières syndrome inherited?

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

ADAR p.Cys976del

c.2926_2928del · rs2101576453 · VCV1362277

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Aicardi-Goutieres syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADAR
Protein: p.Cys976del
Coding: c.2926_2928del
MANE Select: NM_001111
dbSNP: rs2101576453
Type: Deletion
Location: chr1:154588216 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 976: an α-helix; the a to i editase domain

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

Disease context

Aicardi-Goutieres syndrome 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyschromatosis symmetrica hereditaria

For Aicardi-Goutières syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ADAR p.Cys976= Likely benign ★ same residue
ADAR p.Ala813fs Pathogenic/Likely pathogenic ★★ same condition
ADAR p.Ala220_Gly268del Uncertain significance ★★ same condition
ADAR c.2886-11_2886-10del Benign/Likely benign ★★ same condition
ADAR c.2886-1del Likely pathogenic ★ same condition
ADAR p.Arg91fs Pathogenic ★ same condition
ADAR p.Asn857fs Pathogenic ★ same condition
ADAR p.Asp342fs 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-cys976del (accessed [today's date]).

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