Is ADAR p.Val894= (c.2682G>A) pathogenic?

ADAR p.Val894= (c.2682G>A) is classified Benign/Likely benign in ADAR (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 30.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Aicardi-Goutieres syndrome 6.

What condition is associated with ADAR p.Val894= (c.2682G>A)?

ADAR p.Val894= (c.2682G>A) is associated with Aicardi-Goutieres syndrome 6, dyschromatosis symmetrica hereditaria (ClinVar).

How is Aicardi-Goutières syndrome inherited?

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

ADAR p.Val894=

Q: How common is ADAR p.Val894= (c.2682G>A) in the general population?

ADAR p.Val894= (c.2682G>A) is common (popmax 30.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2682G>A · rs1127309 · VCV257474

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 30.4%, afr) — too common for a highly-penetrant pathogenic allele

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP 0.79, phastCons 0.8
Overall
CADD	9.517	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.4% African / African-American · 22,781/74,916 alleles

Filtering AF 30.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.9%

Overall 28.8% 464,774/1,611,136 alleles · common exomes 420,437/1,459,020 · genomes 44,337/152,116 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	33.6%	3
Finnishnot grpmax-eligible	33.1%	3
African / African-Americangrpmax	30.4%	3
European (non-Finnish)	29.5%	3
Remaining individualsnot grpmax-eligible	29.5%	3
Ashkenazi Jewishnot grpmax-eligible	28%	4
East Asian	27%	4
Middle Eastern	26.6%	4
South Asian	23.2%	4
Admixed American	19.1%	5

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val894=
Coding: c.2682G>A
MANE Select: NM_001111
dbSNP: rs1127309
Type: single nucleotide variant
Location: chr1:154589449 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 894: 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 c.2885+1G>A Likely pathogenic ★★ same condition
ADAR p.Arg1078Cys Pathogenic ★★ same condition
ADAR p.Arg1096Ter Pathogenic/Likely pathogenic ★★ same condition
ADAR p.Arg328Ter 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-val894 (accessed [today's date]).

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