Is SPIN4 p.Arg104fs (c.312_313del) pathogenic?

SPIN4 p.Arg104fs (c.312313del) is classified Pathogenic in SPIN4 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-05-30). Very rare (popmax 0.000112%, nfe); Associated with Lui-Jee-Baron syndrome.

What condition is associated with SPIN4 p.Arg104fs (c.312_313del)?

SPIN4 p.Arg104fs (c.312_313del) is associated with Lui-Jee-Baron syndrome (ClinVar).

How common is SPIN4 p.Arg104fs (c.312_313del) in the general population?

SPIN4 p.Arg104fs (c.312_313del) is very rare (popmax 0.000112%, nfe) (gnomAD).

SPIN4 p.Arg104fs

c.312_313del · rs2519642745 · VCV2671851

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

Lui-Jee-Baron syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.7	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,362 alleles

Overall 8.26e-05% 1/1,211,195 alleles · very rare exomes 1/1,098,200 · genomes 0/112,995 · joint denominator

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: SPIN4
Protein: p.Arg104fs
Coding: c.312_313del
MANE Select: NM_001012968
dbSNP: rs2519642745
Type: Microsatellite
Location: chrX:63350507 (GRCh38)
Structure: AlphaFold pLDDT 82.17 · 2 PDB
Residue 104: an α-helix

Full SPIN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Lui-Jee-Baron syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPIN4 p.Val242Asp Uncertain significance ★ ⚠ same condition

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/spin4-p-arg104fs (accessed [today's date]).

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