Is ADRA1B p.Ile60Val (c.178A>G) pathogenic?

ADRA1B p.Ile60Val (c.178A>G) is classified Uncertain significance in ADRA1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). AlphaMissense: likely benign (0.0611); Very rare (popmax 0.000339%, nfe).

How common is ADRA1B p.Ile60Val (c.178A>G) in the general population?

ADRA1B p.Ile60Val (c.178A>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about ADRA1B p.Ile60Val (c.178A>G)?

AlphaMissense predicts likely benign (score 0.0611) — an in-silico prediction, not a clinical call.

ADRA1B p.Ile60Val

c.178A>G · rs2532238424 · VCV2539737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0611 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0611	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -4.99	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 8.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 55 kb · p 0.01 · regional, not allelic
Overall
CADD	21.4	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 0.000339% European (non-Finnish) · 4/1,179,988 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,872 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.Ile60Val
Coding: c.178A>G
MANE Select: NM_000679
dbSNP: rs2532238424
Type: single nucleotide variant
Location: chr5:159917083 (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-ile60val (accessed [today's date]).

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