SCRIB p.Pro1043=
c.3129G>A · rs782560000 · VCV2658913
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0168%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.013 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3 |
| Overall | ||
| CADD | 0.367 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0168%
Middle Eastern · 1/5,966 alleles
Filtering AF
0.007%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00539%
Overall
0.0024%
38/1,580,860 alleles · ultra-rare
exomes 34/1,428,548 · genomes 4/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0168% | 5,966 |
| South Asian | 0.0125% | 7,991 |
| African / African-American | 0.00269% | 37,212 |
| East Asian | 0.00228% | 43,906 |
| European (non-Finnish) | 0.00189% | 52,819 |
| Admixed American | 0.00182% | 54,990 |
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.Pro1043=
- Coding
- c.3129G>A
- MANE Select
- NM_182706
- dbSNP
- rs782560000
- Type
- single nucleotide variant
- Location
- chr8:143803932 (GRCh38)
- Gene constraint
- LOEUF 0.684 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.33 · 42 PDB
- Residue 1043
- a β-strand; the pdz 3 domain; the 'interaction with arhgef7' region; the 'required for interaction with vim' 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.Arg492= 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
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-pro1043 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown