Is ADAR p.Val660fs (c.1979_1980del) pathogenic?

ADAR p.Val660fs (c.19791980del) is classified Pathogenic in ADAR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). Associated with dyschromatosis symmetrica hereditaria.

What condition is associated with ADAR p.Val660fs (c.1979_1980del)?

ADAR p.Val660fs (c.1979_1980del) is associated with dyschromatosis symmetrica hereditaria, Aicardi-Goutieres syndrome 6 (ClinVar).

How is Dyschromatosis symmetrica hereditaria inherited?

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

ADAR p.Val660fs

c.1979_1980del · VCV3758427

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

dyschromatosis symmetrica hereditaria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 5 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: ADAR
Protein: p.Val660fs
Coding: c.1979_1980del
MANE Select: NM_001111
Type: Microsatellite
Location: chr1:154597222 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 660: the drbm 2 domain

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.Phe610del Uncertain significance ★★ same condition
ADAR c.2271-18_2271-17del Likely benign ★★ same condition
ADAR c.2763-10_2763-7del Uncertain significance ★ same condition
ADAR p.Asn711del Uncertain significance ★ same condition
ADAR p.Leu242del Uncertain significance ★ same condition
ADAR p.Leu822del Uncertain significance ★ same condition
ADAR p.Leu855fs Conflicting classifications of pathogenicity ★ ⚠ same condition
ADAR p.Lys359del Uncertain significance ★ 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-val660fs (accessed [today's date]).

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