SCRIB p.Arg492=
c.1476G>T · rs114102220 · VCV791170
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 8.62%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.6 | GERP -3.4 |
| Overall | ||
| CADD | 1.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.62%
African / African-American · 6,467/75,012 alleles
Filtering AF
8.45%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.37%
Overall
0.449%
7,251/1,613,184 alleles · common
exomes 3,543/1,460,890 · genomes 3,708/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.62% | 12 |
| Remaining individualsnot grpmax-eligible | 0.544% | 184 |
| Admixed American | 0.471% | 212 |
| Middle Eastern | 0.314% | 319 |
| Ashkenazi Jewishnot grpmax-eligible | 0.115% | 871 |
| South Asian | 0.0176% | 5,692 |
| European (non-Finnish) | 0.00771% | 12,967 |
| East Asian | 0.00223% | 44,874 |
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.Arg492=
- Coding
- c.1476G>T
- MANE Select
- NM_182706
- dbSNP
- rs114102220
- Type
- single nucleotide variant
- Location
- chr8:143810533 (GRCh38)
- Gene constraint
- LOEUF 0.684 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.33 · 42 PDB
- Residue 492
- the 'sufficient for targeting to adherens junction and to inhibit cell proliferation' region; the 'disordered' region
Similar variants
- 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.Asn647= Benign/Likely benign ★★ same type
- SCRIB p.Leu254= Benign ★★ same type
- SCRIB p.Phe571= Benign ★★ same type
- SCRIB p.Pro1343= Benign ★★ same type
- SCRIB p.Pro1592Leu Likely 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-arg492 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown