Is JUNB p.Arg89Leu (c.266G>T) pathogenic?

JUNB p.Arg89Leu (c.266G>T) is classified Uncertain significance in JUNB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.7684); Very rare (popmax 0.0067%, amr).

How common is JUNB p.Arg89Leu (c.266G>T) in the general population?

JUNB p.Arg89Leu (c.266G>T) is very rare (popmax 0.0067%, amr) (gnomAD).

What do computational predictors say about JUNB p.Arg89Leu (c.266G>T)?

AlphaMissense predicts likely pathogenic (score 0.7684) — an in-silico prediction, not a clinical call.

JUNB p.Arg89Leu

c.266G>T · VCV4040963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.7684	likely pathogenic
REVEL	0.63	indeterminate
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 816 bp · p 0.039 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% Admixed American · 4/59,718 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,611,030 alleles · very rare exomes 4/1,458,810 · genomes 0/152,220 · joint denominator

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: JUNB
Protein: p.Arg89Leu
Coding: c.266G>T
MANE Select: NM_002229
Type: single nucleotide variant
Location: chr19:12792037 (GRCh38)

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

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/junb-p-arg89leu (accessed [today's date]).

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