Is ADAR p.Pro55= (c.165G>A) pathogenic?

ADAR p.Pro55= (c.165G>A) is classified Likely benign in ADAR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-20). Ultra-rare (popmax 0.0253%, sas); Associated with Aicardi-Goutieres syndrome 6.

What condition is associated with ADAR p.Pro55= (c.165G>A)?

ADAR p.Pro55= (c.165G>A) is associated with Aicardi-Goutieres syndrome 6, dyschromatosis symmetrica hereditaria (ClinVar).

How common is ADAR p.Pro55= (c.165G>A) in the general population?

ADAR p.Pro55= (c.165G>A) is ultra-rare (popmax 0.0253%, 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.Pro55=

c.165G>A · rs570176840 · VCV1627632

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Conditions

Aicardi-Goutieres syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.49	GERP -3.4, phastCons 0.84
Overall
CADD	3.633	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% South Asian · 23/91,078 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00285% 46/1,613,932 alleles · ultra-rare exomes 39/1,461,740 · genomes 7/152,192 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
African / African-American	0.00667%	14,982
Remaining individualsnot grpmax-eligible	0.0048%	20,825
East Asian	0.00223%	44,898
European (non-Finnish)	0.00119%	84,283

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.Pro55=
Coding: c.165G>A
MANE Select: NM_001111
dbSNP: rs570176840
Type: single nucleotide variant
Location: chr1:154602477 (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

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.Pro55Leu 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-pro55 (accessed [today's date]).

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