Is JUND p.Pro345Ser (c.1033C>T) pathogenic?

JUND p.Pro345Ser (c.1033C>T) is classified Uncertain significance in JUND (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.2098); Ultra-rare (popmax 0.0327%, sas).

How common is JUND p.Pro345Ser (c.1033C>T) in the general population?

JUND p.Pro345Ser (c.1033C>T) is ultra-rare (popmax 0.0327%, sas) (gnomAD).

What do computational predictors say about JUND p.Pro345Ser (c.1033C>T)?

AlphaMissense predicts likely benign (score 0.2098) — an in-silico prediction, not a clinical call.

JUND p.Pro345Ser

c.1033C>T · VCV3862346

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2098 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0327%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2098	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -6.37	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 6.1	GERP -0.35, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 86 bp · p 0.42 · regional, not allelic
Overall
CADD	23.0	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 0.0327% South Asian · 28/85,728 alleles

Filtering AF 0.0232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.02%

Overall 0.00193% 30/1,557,716 alleles · ultra-rare exomes 29/1,405,532 · genomes 1/152,184 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0327%	3,062
Remaining individualsnot grpmax-eligible	0.00332%	30,150

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: JUND
Protein: p.Pro345Ser
Coding: c.1033C>T
MANE Select: NM_005354
Type: single nucleotide variant
Location: chr19:18280452 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 64.42 · 10 PDB

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

Similar variants

JUND p.Ala159Gly Uncertain significance ★ ⚠ same type
JUND p.Ala160Thr Uncertain significance ★ ⚠ same type
JUND p.Ala161Thr Uncertain significance ★ ⚠ same type
JUND p.Ala163Gly Uncertain significance ★ ⚠ same type
JUND p.Ala163Ser Uncertain significance ★ ⚠ same type
JUND p.Ala204Val Uncertain significance ★ ⚠ same type
JUND p.Ala216Pro Uncertain significance ★ ⚠ same type
JUND p.Ala216Val 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/jund-p-pro345ser (accessed [today's date]).

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