Is ADAR p.Pro193fs (c.578del) pathogenic?

ADAR p.Pro193fs (c.578del) is classified Pathogenic in ADAR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). Very rare (popmax 8.47e-05%, nfe); Associated with Aicardi-Goutieres syndrome 6.

What condition is associated with ADAR p.Pro193fs (c.578del)?

ADAR p.Pro193fs (c.578del) is associated with Aicardi-Goutieres syndrome 6, dyschromatosis symmetrica hereditaria (ClinVar).

How common is ADAR p.Pro193fs (c.578del) in the general population?

ADAR p.Pro193fs (c.578del) is very rare (popmax 8.47e-05%, nfe) (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.Pro193fs

c.578del · VCV4784878

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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

Conditions

Aicardi-Goutieres syndrome 6

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 2 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 0.67, phastCons 0.37

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% 1/1,461,892 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.Pro193fs
Coding: c.578del
MANE Select: NM_001111
Type: Deletion
Location: chr1:154602064 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 193: the z-binding 1 domain; a UniProt-annotated variant site (in ags6); the 'interaction with z-dna' region

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.Pro193Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
ADAR p.Pro193Leu Uncertain significance ★ ⚠ same residue
ADAR p.Pro193Thr Uncertain significance ★ ⚠ 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

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-pro193fs (accessed [today's date]).

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