Is ADARB1 p.Ser486Phe (c.1457C>T) pathogenic?

ADARB1 p.Ser486Phe (c.1457C>T) is classified Uncertain significance in ADARB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely pathogenic (0.9901); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ADARB1 p.Ser486Phe (c.1457C>T)?

ADARB1 p.Ser486Phe (c.1457C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADARB1 p.Ser486Phe (c.1457C>T) in the general population?

ADARB1 p.Ser486Phe (c.1457C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADARB1 p.Ser486Phe (c.1457C>T)?

AlphaMissense predicts likely pathogenic (score 0.9901) — an in-silico prediction, not a clinical call.

ADARB1 p.Ser486Phe

c.1457C>T · rs2518026134 · VCV2480838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9901 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9901	likely pathogenic
REVEL	0.912	moderately pathogenic-leaning
SaProt	LLR -9.86	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 42 kb · p 1.8e-22 · regional, not allelic
Overall
CADD	26.1	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 S526F vs ClinVar S486F) — verify the residue.

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: ADARB1
Protein: p.Ser486Phe
Coding: c.1457C>T
MANE Select: NM_001112
dbSNP: rs2518026134
Type: single nucleotide variant
Location: chr21:45184983 (GRCh38)
Gene constraint: LOEUF 0.323 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.12 · 13 PDB
Residue 486: the a to i editase domain; the 'disordered' region

Full ADARB1 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

ADARB1 p.Pro345Leu Uncertain significance ★★ ⚠ same condition
ADARB1 p.Ala497Thr Uncertain significance ★ ⚠ same condition
ADARB1 p.Ala608Thr Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg20His Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg244His Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg287Gln Uncertain significance ★ same condition
ADARB1 p.Arg287Leu Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg329Cys 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-ser486phe (accessed [today's date]).

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