Is ADAR p.Ala735= (c.2205C>T) pathogenic?

ADAR p.Ala735= (c.2205C>T) is classified Likely benign in ADAR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-06). Very rare (popmax 0.00167%, amr); Associated with Aicardi-Goutieres syndrome 6.

What condition is associated with ADAR p.Ala735= (c.2205C>T)?

ADAR p.Ala735= (c.2205C>T) is associated with Aicardi-Goutieres syndrome 6, dyschromatosis symmetrica hereditaria (ClinVar).

How common is ADAR p.Ala735= (c.2205C>T) in the general population?

ADAR p.Ala735= (c.2205C>T) is very rare (popmax 0.00167%, amr) (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.Ala735=

c.2205C>T · rs1697533791 · VCV1643195

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -0.094	GERP -3.8, phastCons 0.12
Overall
CADD	8.615	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Overall 6.84e-05% 1/1,461,852 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.Ala735=
Coding: c.2205C>T
MANE Select: NM_001111
dbSNP: rs1697533791
Type: single nucleotide variant
Location: chr1:154596870 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 735: the drbm 3 domain; an α-helix

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.Ala735Thr Uncertain significance ★★ ⚠ same residue
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

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-ala735 (accessed [today's date]).

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