Is ADAR p.Arg1175= (c.3523A>C) pathogenic?

ADAR p.Arg1175= (c.3523A>C) is classified Benign/Likely benign in ADAR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-19). Rare (popmax 0.507%, sas); Associated with Aicardi-Goutieres syndrome 6.

What condition is associated with ADAR p.Arg1175= (c.3523A>C)?

ADAR p.Arg1175= (c.3523A>C) is associated with Aicardi-Goutieres syndrome 6, dyschromatosis symmetrica hereditaria (ClinVar).

How common is ADAR p.Arg1175= (c.3523A>C) in the general population?

ADAR p.Arg1175= (c.3523A>C) is rare (popmax 0.507%, sas) (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.Arg1175=

c.3523A>C · rs146625055 · VCV292758

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.507%, sas)

Conditions

Aicardi-Goutieres syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.51	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 2.9	GERP 1.7, phastCons 1
Overall
CADD	16.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.507% South Asian · 462/91,082 alleles

Filtering AF 0.469% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.454%

Overall 0.0528% 852/1,614,192 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.507%	197
Amishnot grpmax-eligible	0.219%	456
Middle Eastern	0.198%	505
Admixed American	0.12%	834
Remaining individualsnot grpmax-eligible	0.0592%	1,689
European (non-Finnish)	0.0219%	4,574
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,935
Finnishnot grpmax-eligible	0.00312%	32,016
East Asian	0.00223%	44,888

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.Arg1175=
Coding: c.3523A>C
MANE Select: NM_001111
dbSNP: rs146625055
Type: single nucleotide variant
Location: chr1:154584964 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 1175: 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-arg1175 (accessed [today's date]).

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