Is JUN p.Val130Ala (c.389T>C) pathogenic?

JUN p.Val130Ala (c.389T>C) is classified Uncertain significance in JUN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). AlphaMissense: likely benign (0.1742); Very rare (popmax 0.00169%, amr).

How common is JUN p.Val130Ala (c.389T>C) in the general population?

JUN p.Val130Ala (c.389T>C) is very rare (popmax 0.00169%, amr) (gnomAD).

What do computational predictors say about JUN p.Val130Ala (c.389T>C)?

AlphaMissense predicts likely benign (score 0.1742) — an in-silico prediction, not a clinical call.

JUN p.Val130Ala

c.389T>C · VCV3862340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1742 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1742	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -5.39	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 7.6	GERP -0.37, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 313 bp · p 0.14 · regional, not allelic
Overall
CADD	21.1	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 0.00169% Admixed American · 1/59,258 alleles

Filtering AF 0.000432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000315%

Overall 0.000817% 13/1,591,224 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00169%	59,258
Remaining individualsnot grpmax-eligible	0.00162%	61,720
African / African-American	0.00134%	74,756
European (non-Finnish)	0.000853%	117,199

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: JUN
Protein: p.Val130Ala
Coding: c.389T>C
MANE Select: NM_002228
Type: single nucleotide variant
Location: chr1:58782682 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 62.45 · 10 PDB

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

Similar variants

JUN p.Ala148Val Uncertain significance ★ ⚠ same type
JUN p.Ala161Ser Uncertain significance ★ ⚠ same type
JUN p.Ala187Ser Uncertain significance ★ ⚠ same type
JUN p.Ala224Gly Uncertain significance ★ ⚠ same type
JUN p.Asn175Asp Uncertain significance ★ ⚠ same type
JUN p.Asn314Lys Uncertain significance ★ ⚠ same type
JUN p.Gln218Arg Uncertain significance ★ ⚠ same type
JUN p.Gln290Arg 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/jun-p-val130ala (accessed [today's date]).

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