Is JUNB p.Tyr215Phe (c.644A>T) pathogenic?

JUNB p.Tyr215Phe (c.644A>T) is classified Uncertain significance in JUNB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.4155); Absent from gnomAD v4.1.

How common is JUNB p.Tyr215Phe (c.644A>T) in the general population?

JUNB p.Tyr215Phe (c.644A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about JUNB p.Tyr215Phe (c.644A>T)?

AlphaMissense predicts ambiguous (score 0.4155) — an in-silico prediction, not a clinical call.

JUNB p.Tyr215Phe

c.644A>T · VCV4680538

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4155 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4155	ambiguous
REVEL	0.165	moderately benign-leaning
SaProt	LLR -8.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP -1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 816 bp · p 0.039 · regional, not allelic
Overall
CADD	23.0	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

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: JUNB
Protein: p.Tyr215Phe
Coding: c.644A>T
MANE Select: NM_002229
Type: single nucleotide variant
Location: chr19:12792415 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI 0.23 (gnomAD)
Structure: AlphaFold pLDDT 61.35

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

Similar variants

JUNB p.Ala236Thr Uncertain significance ★ ⚠ same type
JUNB p.Ala249Val Uncertain significance ★ ⚠ same type
JUNB p.Arg250His Uncertain significance ★ ⚠ same type
JUNB p.Glu267Gly Uncertain significance ★ ⚠ same type
JUNB p.His218Arg Uncertain significance ★ ⚠ same type
JUNB p.Ile261Val Uncertain significance ★ ⚠ same type
JUNB p.Leu230Pro Uncertain significance ★ ⚠ same type
JUNB p.Met329Leu 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/junb-p-tyr215phe (accessed [today's date]).

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