Is ADAR p.Pro351Arg (c.1052C>G) pathogenic?

ADAR p.Pro351Arg (c.1052C>G) is classified Uncertain significance in ADAR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: ambiguous (0.3985); Absent from gnomAD v4.1; Associated with dyschromatosis symmetrica hereditaria.

What condition is associated with ADAR p.Pro351Arg (c.1052C>G)?

ADAR p.Pro351Arg (c.1052C>G) is associated with dyschromatosis symmetrica hereditaria, Aicardi-Goutieres syndrome 6 (ClinVar).

How common is ADAR p.Pro351Arg (c.1052C>G) in the general population?

ADAR p.Pro351Arg (c.1052C>G) 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.

What do computational predictors say about ADAR p.Pro351Arg (c.1052C>G)?

AlphaMissense predicts ambiguous (score 0.3985) — an in-silico prediction, not a clinical call.

ADAR p.Pro351Arg

c.1052C>G · VCV3758165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dyschromatosis symmetrica hereditaria

Computational evidence

Protein change
AlphaMissense	0.3985	ambiguous
REVEL	0.513	indeterminate
SaProt	LLR -10.01	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 0.65, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,556 bp · p 0.34 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro351Arg
Coding: c.1052C>G
MANE Select: NM_001111
Type: single nucleotide variant
Location: chr1:154601590 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 351: the z-binding 2 domain

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.Pro351Ser 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-pro351arg (accessed [today's date]).

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