Is JUN p.Ala161Ser (c.481G>T) pathogenic?

JUN p.Ala161Ser (c.481G>T) is classified Uncertain significance in JUN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0598); Absent from gnomAD v4.1.

How common is JUN p.Ala161Ser (c.481G>T) in the general population?

JUN p.Ala161Ser (c.481G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about JUN p.Ala161Ser (c.481G>T)?

AlphaMissense predicts likely benign (score 0.0598) — an in-silico prediction, not a clinical call.

JUN p.Ala161Ser

c.481G>T · VCV4089530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0598 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,920)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0598	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -5.61	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 2.5	GERP 0.18, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 313 bp · p 0.14 · regional, not allelic
Overall
CADD	14.45	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

No allele count reported in gnomAD v4.1 (AN 1,576,920). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: JUN
Protein: p.Ala161Ser
Coding: c.481G>T
MANE Select: NM_002228
Type: single nucleotide variant
Location: chr1:58782590 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 62.45 · 10 PDB
Residue 161: the 'interaction with page4' region

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.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
JUN p.Gln290Glu 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-ala161ser (accessed [today's date]).

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