SCRIB p.Leu1404=
c.4212G>A · rs115360394 · VCV3039866
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.95%, afr)
Conditions
1
SCRIB-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.012 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.059 | GERP -2.4, phastCons 0.61 |
| Overall | ||
| CADD | 1.764 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.95%
African / African-American · 712/74,958 alleles
Filtering AF
0.892%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.869%
Overall
0.0505%
803/1,591,602 alleles · rare
exomes 403/1,439,264 · genomes 400/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.95% | 105 |
| Remaining individualsnot grpmax-eligible | 0.0645% | 1,551 |
| Middle Eastern | 0.0496% | 2,015 |
| Admixed American | 0.0477% | 2,096 |
| South Asian | 0.00335% | 29,807 |
| European (non-Finnish) | 0.00145% | 69,189 |
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
- SCRIB
- Protein
- p.Leu1404=
- Coding
- c.4212G>A
- MANE Select
- NM_182706
- dbSNP
- rs115360394
- Type
- single nucleotide variant
- Location
- chr8:143792601 (GRCh38)
- Gene constraint
- LOEUF 0.684 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.33 · 42 PDB
- Residue 1404
- the 'disordered' region
Disease context
SCRIB-related disorder
Similar variants
- SCRIB p.Arg231Gln Uncertain significance ★ ⚠ same condition
- SCRIB c.2179-10C>T Likely benign same condition
- SCRIB c.3714+7G>A Likely benign same condition
- SCRIB c.4018-6C>T Likely benign same condition
- SCRIB c.4514+8C>T Likely benign same condition
- SCRIB c.4515-4G>A Likely benign same condition
- SCRIB c.907-4C>G Likely benign same condition
- SCRIB c.907-4C>T Likely benign 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/scrib-p-leu1404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown