Is ADARB2 p.Leu165Phe (c.493C>T) pathogenic?

ADARB2 p.Leu165Phe (c.493C>T) is classified Uncertain significance in ADARB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1139); Absent from gnomAD v4.1.

How common is ADARB2 p.Leu165Phe (c.493C>T) in the general population?

ADARB2 p.Leu165Phe (c.493C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADARB2 p.Leu165Phe (c.493C>T)?

AlphaMissense predicts likely benign (score 0.1139) — an in-silico prediction, not a clinical call.

ADARB2 p.Leu165Phe

c.493C>T · rs1832283581 · VCV3080447

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1139 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1139	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -8.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP -0.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 554 kb · p 0.84 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: ADARB2
Protein: p.Leu165Phe
Coding: c.493C>T
MANE Select: NM_018702
dbSNP: rs1832283581
Type: single nucleotide variant
Location: chr10:1363612 (GRCh38)
Gene constraint: LOEUF 0.681 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.69
Residue 165: the drbm 1 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-leu165phe (accessed [today's date]).

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