Is ADRA1B p.Tyr82Phe (c.245A>T) pathogenic?

ADRA1B p.Tyr82Phe (c.245A>T) is classified Uncertain significance in ADRA1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely benign (0.1438); Very rare (popmax 8.47e-05%, nfe).

How common is ADRA1B p.Tyr82Phe (c.245A>T) in the general population?

ADRA1B p.Tyr82Phe (c.245A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ADRA1B p.Tyr82Phe (c.245A>T)?

AlphaMissense predicts likely benign (score 0.1438) — an in-silico prediction, not a clinical call.

ADRA1B p.Tyr82Phe

c.245A>T · VCV3502095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1438 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1438	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 55 kb · p 0.01 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,956 alleles

Overall 6.84e-05% 1/1,461,876 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: ADRA1B
Protein: p.Tyr82Phe
Coding: c.245A>T
MANE Select: NM_000679
Type: single nucleotide variant
Location: chr5:159917150 (GRCh38)
Gene constraint: LOEUF 1.449 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.95

Full ADRA1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADRA1B p.Ala188Thr Uncertain significance ★ ⚠ same type
ADRA1B p.Ala217Val Uncertain significance ★ ⚠ same type
ADRA1B p.Ala449Thr Uncertain significance ★ ⚠ same type
ADRA1B p.Ala503Thr Uncertain significance ★ ⚠ same type
ADRA1B p.Ala516Glu Uncertain significance ★ ⚠ same type
ADRA1B p.Ala54Pro Uncertain significance ★ ⚠ same type
ADRA1B p.Ala90Asp Uncertain significance ★ ⚠ same type
ADRA1B p.Arg115Gln Uncertain significance ★ ⚠ 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/adra1b-p-tyr82phe (accessed [today's date]).

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