Is ADARB1 p.Ala682Val (c.2045C>T) pathogenic?

ADARB1 p.Ala682Val (c.2045C>T) is classified Pathogenic in ADARB1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-04-30). AlphaMissense: ambiguous (0.5614); Very rare (popmax 8.48e-05%, nfe); Associated with neurodevelopmental disorder with hypotonia, microcephaly, and seizures.

What condition is associated with ADARB1 p.Ala682Val (c.2045C>T)?

ADARB1 p.Ala682Val (c.2045C>T) is associated with neurodevelopmental disorder with hypotonia, microcephaly, and seizures (ClinVar).

How common is ADARB1 p.Ala682Val (c.2045C>T) in the general population?

ADARB1 p.Ala682Val (c.2045C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ADARB1 p.Ala682Val (c.2045C>T)?

AlphaMissense predicts ambiguous (score 0.5614) — an in-silico prediction, not a clinical call.

ADARB1 p.Ala682Val

c.2045C>T · rs1323703791 · VCV870453

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5614 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

neurodevelopmental disorder with hypotonia, microcephaly, and seizures

Computational evidence

Protein change
AlphaMissense	0.5614	ambiguous
REVEL	0.711	pathogenic-leaning
SaProt	LLR -11.47	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.98	donor gain · deltas
Pangolin	Δ0.88	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 42 kb · p 1.8e-22 · regional, not allelic
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A722V vs ClinVar A682V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,710 alleles

Overall 6.86e-05% 1/1,458,178 alleles · very rare

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: ADARB1
Protein: p.Ala682Val
Coding: c.2045C>T
MANE Select: NM_001112
dbSNP: rs1323703791
Type: single nucleotide variant
Location: chr21:45222136 (GRCh38)
Gene constraint: LOEUF 0.323 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.12 · 13 PDB
Residue 682: the a to i editase domain

Full ADARB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with hypotonia, microcephaly, and seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADARB1 c.1397-354A>G Uncertain significance ★★ ⚠ same condition
ADARB1 p.Gly553Arg Uncertain significance ★★ ⚠ same condition
ADARB1 p.Lys654= Benign ★★ same condition
ADARB1 c.1565+9350C>A Uncertain significance ★ same condition
ADARB1 c.-48+18228C>T Uncertain significance ★ same condition
ADARB1 p.Arg481Gln Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg66Cys Uncertain significance ★ ⚠ same condition
ADARB1 p.Gly276Val 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/adarb1-p-ala682val (accessed [today's date]).

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