Is ADAR p.Ala813fs (c.2433_2434del) pathogenic?

ADAR p.Ala813fs (c.24332434del) is classified Pathogenic/Likely pathogenic in ADAR (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-11-08). Very rare (popmax 0.00268%, afr); Associated with ADAR-related disorder.

What condition is associated with ADAR p.Ala813fs (c.2433_2434del)?

ADAR p.Ala813fs (c.2433_2434del) is associated with ADAR-related disorder, dyschromatosis symmetrica hereditaria, Aicardi-Goutieres syndrome 6 (ClinVar).

How common is ADAR p.Ala813fs (c.2433_2434del) in the general population?

ADAR p.Ala813fs (c.2433_2434del) is very rare (popmax 0.00268%, afr) (gnomAD).

ADAR p.Ala813fs

c.2433_2434del · rs779357448 · VCV521470

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Conditions

ADAR-related disorder

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 7 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 0.93, phastCons 1
Overall
CADD	34.0	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 0.00268% African / African-American · 2/74,754 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00118% 19/1,613,700 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,377
East Asian	0.00223%	44,856
European (non-Finnish)	0.00127%	78,667
South Asian	0.0011%	91,062

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.Ala813fs
Coding: c.2433_2434del
MANE Select: NM_001111
dbSNP: rs779357448
Type: Deletion
Location: chr1:154590246 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB

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

Disease context

ADAR-related disorder

Also linked: dyschromatosis symmetrica hereditaria Aicardi-Goutieres syndrome 6 ADAR-related type 1 interferonopathy

Similar variants

ADAR p.Ala813Thr Uncertain significance ★ ⚠ same residue
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
ADAR p.Glu598fs 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-ala813fs (accessed [today's date]).

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