Is ADARB2 p.Val394Ile (c.1180G>A) pathogenic?

ADARB2 p.Val394Ile (c.1180G>A) is classified Uncertain significance in ADARB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0968); Very rare (popmax 0.00333%, amr).

How common is ADARB2 p.Val394Ile (c.1180G>A) in the general population?

ADARB2 p.Val394Ile (c.1180G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ADARB2 p.Val394Ile (c.1180G>A)?

AlphaMissense predicts likely benign (score 0.0968) — an in-silico prediction, not a clinical call.

ADARB2 p.Val394Ile

c.1180G>A · rs780188177 · VCV3080320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0968 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0968	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -10.27	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 3.2	GERP -0.95, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 554 kb · p 0.84 · regional, not allelic
Overall
CADD	23.1	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 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00173% 28/1,613,946 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,996
European (non-Finnish)	0.00203%	49,166
Remaining individualsnot grpmax-eligible	0.0016%	62,484
South Asian	0.0011%	91,040

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.Val394Ile
Coding: c.1180G>A
MANE Select: NM_018702
dbSNP: rs780188177
Type: single nucleotide variant
Location: chr10:1270967 (GRCh38)
Gene constraint: LOEUF 0.681 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.69

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-val394ile (accessed [today's date]).

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