SCRIB p.Thr1185=
c.3555C>T · rs142247868 · VCV3034499
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.02%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.023 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.2 | GERP -3 |
| Overall | ||
| CADD | 0.562 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.02%
African / African-American · 766/74,948 alleles
Filtering AF
0.962%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.938%
Overall
0.0755%
1,205/1,596,018 alleles · low-frequency
exomes 722/1,443,710 · genomes 483/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.02% | 98 |
| Middle Eastern | 0.226% | 442 |
| Admixed American | 0.176% | 567 |
| Remaining individualsnot grpmax-eligible | 0.108% | 927 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0919% | 1,089 |
| South Asian | 0.0333% | 3,005 |
| European (non-Finnish) | 0.0167% | 5,976 |
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.Thr1185=
- Coding
- c.3555C>T
- MANE Select
- NM_182706
- dbSNP
- rs142247868
- Type
- single nucleotide variant
- Location
- chr8:143803431 (GRCh38)
- Gene constraint
- LOEUF 0.684 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.33 · 42 PDB
- Residue 1185
- a β-strand; the pdz 4 domain; the 'interaction with arhgef7' region; the 'required for interaction with vim' region
Similar variants
- SCRIB p.Thr1185Ala 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.Leu254= Benign ★★ same type
- SCRIB p.Phe571= 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-thr1185 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown