SCRIB p.Leu254=
c.760C>T · rs144565607 · VCV713861
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.28%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.43 | GERP -3.6, phastCons 0.002 |
| Overall | ||
| CADD | 1.963 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.28%
European (non-Finnish) · 15,072/1,179,666 alleles
Filtering AF
1.26%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.25%
Overall
1.09%
17,457/1,604,468 alleles · low-frequency
exomes 16,233/1,452,118 · genomes 1,224/152,350 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.28% | 78 |
| Ashkenazi Jewishnot grpmax-eligible | 1.06% | 95 |
| Remaining individualsnot grpmax-eligible | 0.96% | 104 |
| Admixed American | 0.868% | 115 |
| Middle Eastern | 0.661% | 151 |
| Finnishnot grpmax-eligible | 0.511% | 196 |
| South Asian | 0.509% | 196 |
| African / African-American | 0.212% | 472 |
| Amishnot grpmax-eligible | 0.11% | 912 |
| East Asian | 0.0178% | 5,608 |
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.Leu254=
- Coding
- c.760C>T
- MANE Select
- NM_182706
- dbSNP
- rs144565607
- Type
- single nucleotide variant
- Location
- chr8:143812844 (GRCh38)
- Gene constraint
- LOEUF 0.684 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.33 · 42 PDB
- Residue 254
- the 'sufficient for targeting to adherens junction and to inhibit cell proliferation' region
Similar variants
- SCRIB p.Leu254Val Uncertain significance ★ ⚠ same residue
- SCRIB c.3120+10C>G Benign/Likely benign ★★ same type
- SCRIB c.504-9C>T Benign ★★ same type
- SCRIB p.Ala1488= Likely benign ★★ same type
- SCRIB p.Arg492= Benign ★★ same type
- SCRIB p.Asn647= Benign/Likely benign ★★ same type
- SCRIB p.Phe571= Benign ★★ same type
- SCRIB p.Pro1343= Benign ★★ 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/scrib-p-leu254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown