Is ADAR p.Pro694= (c.2082T>A) pathogenic?

ADAR p.Pro694= (c.2082T>A) is classified Uncertain significance in ADAR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). Absent from gnomAD v4.1; Associated with dyschromatosis symmetrica hereditaria.

What condition is associated with ADAR p.Pro694= (c.2082T>A)?

ADAR p.Pro694= (c.2082T>A) is associated with dyschromatosis symmetrica hereditaria, Aicardi-Goutieres syndrome 6 (ClinVar).

How common is ADAR p.Pro694= (c.2082T>A) in the general population?

ADAR p.Pro694= (c.2082T>A) is absent from gnomAD v4.1 (gnomAD).

How is Dyschromatosis symmetrica hereditaria inherited?

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

ADAR p.Pro694=

c.2082T>A · rs1349730104 · VCV2006135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dyschromatosis symmetrica hereditaria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.57	acceptor gain · deltas
Pangolin	Δ0.29	gain · loss 0.14 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -8.3	GERP -3.8
Overall
CADD	0.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADAR
Protein: p.Pro694=
Coding: c.2082T>A
MANE Select: NM_001111
dbSNP: rs1349730104
Type: single nucleotide variant
Location: chr1:154596993 (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

dyschromatosis symmetrica hereditaria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Aicardi-Goutieres syndrome 6

For Dyschromatosis symmetrica hereditaria (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

ADAR p.Pro694Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro694 (accessed [today's date]).

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