Is ADAR p.Val259Met (c.775G>A) pathogenic?

ADAR p.Val259Met (c.775G>A) is classified Uncertain significance in ADAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.1105); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ADAR p.Val259Met (c.775G>A)?

ADAR p.Val259Met (c.775G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ADAR p.Val259Met (c.775G>A) in the general population?

ADAR p.Val259Met (c.775G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAR p.Val259Met (c.775G>A)?

AlphaMissense predicts likely benign (score 0.1105) — an in-silico prediction, not a clinical call.

ADAR p.Val259Met

c.775G>A · VCV4538678

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1105 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1105	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -10.47	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -2.1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,556 bp · p 0.34 · regional, not allelic
Overall
CADD	13.43	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.Val259Met
Coding: c.775G>A
MANE Select: NM_001111
Type: single nucleotide variant
Location: chr1:154601867 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 24 PDB
Residue 259: the 'disordered' region

Full ADAR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADAR p.Ala515Thr Uncertain significance ★★ ⚠ same condition
ADAR p.Ala549Gly Uncertain significance ★★ ⚠ same condition
ADAR p.Ala787Val Uncertain significance ★★ ⚠ same condition
ADAR p.Arg1150Gln Uncertain significance ★★ ⚠ same condition
ADAR p.Arg360Gln Uncertain significance ★★ ⚠ same condition
ADAR p.Arg474Gln Uncertain significance ★★ ⚠ same condition
ADAR p.Arg790His Uncertain significance ★★ ⚠ same condition
ADAR p.Arg850Trp Uncertain significance ★★ ⚠ 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-val259met (accessed [today's date]).

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