Is JUNB p.Pro227Gln (c.680C>A) pathogenic?

JUNB p.Pro227Gln (c.680C>A) is classified Uncertain significance in JUNB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). AlphaMissense: likely benign (0.1064); Ultra-rare (popmax 0.0147%, afr).

How common is JUNB p.Pro227Gln (c.680C>A) in the general population?

JUNB p.Pro227Gln (c.680C>A) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about JUNB p.Pro227Gln (c.680C>A)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

JUNB p.Pro227Gln

c.680C>A · VCV3531603

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP -3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 816 bp · p 0.039 · regional, not allelic
Overall
CADD	21.3	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 0.0147% African / African-American · 11/74,846 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00075% 12/1,600,822 alleles · ultra-rare exomes 6/1,448,614 · genomes 6/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,804
Remaining individualsnot grpmax-eligible	0.00161%	61,988

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.Pro227Gln
Coding: c.680C>A
MANE Select: NM_002229
Type: single nucleotide variant
Location: chr19:12792451 (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.Pro227Ser Uncertain significance ★ ⚠ same residue
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

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-pro227gln (accessed [today's date]).

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