Is ADAR p.Phe852Val (c.2554T>G) pathogenic?

ADAR p.Phe852Val (c.2554T>G) is classified Uncertain significance in ADAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-15). AlphaMissense: likely pathogenic (0.9538); Absent from gnomAD v4.1; Associated with Aicardi-Goutieres syndrome 6.

What condition is associated with ADAR p.Phe852Val (c.2554T>G)?

ADAR p.Phe852Val (c.2554T>G) is associated with Aicardi-Goutieres syndrome 6, dyschromatosis symmetrica hereditaria (ClinVar).

How common is ADAR p.Phe852Val (c.2554T>G) in the general population?

ADAR p.Phe852Val (c.2554T>G) is absent from gnomAD v4.1 (gnomAD).

How is Aicardi-Goutières syndrome inherited?

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

What do computational predictors say about ADAR p.Phe852Val (c.2554T>G)?

AlphaMissense predicts likely pathogenic (score 0.9538) — an in-silico prediction, not a clinical call.

ADAR p.Phe852Val

c.2554T>G · rs2101585739 · VCV1522348

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9538 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Aicardi-Goutieres syndrome 6

Computational evidence

Protein change
AlphaMissense	0.9538	likely pathogenic
REVEL	0.636	indeterminate
SaProt	LLR -13.97	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 17 kb · p 1.3e-17 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Phe852Val
Coding: c.2554T>G
MANE Select: NM_001111
dbSNP: rs2101585739
Type: single nucleotide variant
Location: chr1:154589871 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 852: 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 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-phe852val (accessed [today's date]).

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