Is SPIN4 p.Val242Asp (c.725T>A) pathogenic?

SPIN4 p.Val242Asp (c.725T>A) is classified Uncertain significance in SPIN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). AlphaMissense: likely pathogenic (0.9872); Absent from gnomAD v4.1; Associated with Lui-Jee-Baron syndrome.

What condition is associated with SPIN4 p.Val242Asp (c.725T>A)?

SPIN4 p.Val242Asp (c.725T>A) is associated with Lui-Jee-Baron syndrome (ClinVar).

How common is SPIN4 p.Val242Asp (c.725T>A) in the general population?

SPIN4 p.Val242Asp (c.725T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SPIN4 p.Val242Asp (c.725T>A)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

SPIN4 p.Val242Asp

c.725T>A · VCV3899282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Lui-Jee-Baron syndrome

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic · top 5% in SPIN4
REVEL	0.643	indeterminate
SaProt	LLR -12.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 746 bp · p 2.5e-07 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: SPIN4
Protein: p.Val242Asp
Coding: c.725T>A
MANE Select: NM_001012968
Type: single nucleotide variant
Location: chrX:63350095 (GRCh38)
Structure: AlphaFold pLDDT 82.17 · 2 PDB
Residue 242: a β-strand; the 'tudor-like domain 3' region

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.Arg104fs Pathogenic ★ same condition
SPIN4 p.Arg144Leu Uncertain significance ★ ⚠ same type
SPIN4 p.Arg37Gly Uncertain significance ★ ⚠ same type
SPIN4 p.Arg38Lys Uncertain significance ★ ⚠ same type
SPIN4 p.His207Gln Uncertain significance ★ ⚠ same type
SPIN4 p.Met148Ile Uncertain significance ★ ⚠ same type
SPIN4 p.Ser117Cys Uncertain significance ★ ⚠ same type
SPIN4 p.Ser2Tyr 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/spin4-p-val242asp (accessed [today's date]).

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