Is ADARB2 p.Arg287Cys (c.859C>T) pathogenic?

ADARB2 p.Arg287Cys (c.859C>T) is classified Uncertain significance in ADARB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-21). AlphaMissense: ambiguous (0.4504); Very rare (popmax 0.00174%, sas).

How common is ADARB2 p.Arg287Cys (c.859C>T) in the general population?

ADARB2 p.Arg287Cys (c.859C>T) is very rare (popmax 0.00174%, sas) (gnomAD).

What do computational predictors say about ADARB2 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts ambiguous (score 0.4504) — an in-silico prediction, not a clinical call.

ADARB2 p.Arg287Cys

c.859C>T · VCV4011123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00174%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4504	ambiguous
REVEL	0.745	pathogenic-leaning
SaProt	LLR -10.51	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 554 kb · p 0.84 · regional, not allelic
Overall
CADD	27.7	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

Grpmax group 0.00174% South Asian · 1/57,368 alleles

Overall 0.000166% 2/1,206,088 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00174%	57,368
European (non-Finnish)	9.51e-05%	1,051,370

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: ADARB2
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_018702
Type: single nucleotide variant
Location: chr10:1363246 (GRCh38)
Gene constraint: LOEUF 0.681 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.69
Residue 287: the drbm 2 domain

Full ADARB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADARB2 p.Arg457His Uncertain significance ★★ ⚠ same type
ADARB2 p.Arg457Ser Uncertain significance ★★ ⚠ same type
ADARB2 p.Ala125= Likely benign ★★ same type
ADARB2 p.Arg328= Benign ★★ same type
ADARB2 p.Arg657Gln Benign ★★ same type
ADARB2 p.Glu300Lys Benign ★★ ⚠ same type
ADARB2 p.Ser463= Benign ★★ same type
ADARB2 p.Val155= Benign ★★ same type

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/adarb2-p-arg287cys (accessed [today's date]).

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