Is JUN p.Leu173Val (c.517C>G) pathogenic?

JUN p.Leu173Val (c.517C>G) is classified Uncertain significance in JUN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely pathogenic (0.7555); Absent from gnomAD v4.1.

How common is JUN p.Leu173Val (c.517C>G) in the general population?

JUN p.Leu173Val (c.517C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about JUN p.Leu173Val (c.517C>G)?

AlphaMissense predicts likely pathogenic (score 0.7555) — an in-silico prediction, not a clinical call.

JUN p.Leu173Val

c.517C>G · VCV4040962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7555 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7555	likely pathogenic
REVEL	0.452	indeterminate
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 313 bp · p 0.14 · regional, not allelic
Overall
CADD	26.0	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: JUN
Protein: p.Leu173Val
Coding: c.517C>G
MANE Select: NM_002228
Type: single nucleotide variant
Location: chr1:58782554 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 62.45 · 10 PDB
Residue 173: 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.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-leu173val (accessed [today's date]).

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