SCRIB p.Ala1578Ser
c.4732G>T · rs1554632692 · VCV3158696
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0045%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.117 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.26 | acceptor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 1.13 | unconstrained · MANE · 20 kb · p 9.1e-08 · regional, not allelic |
| Overall | ||
| CADD | 28.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0045%
East Asian · 2/44,460 alleles
Filtering AF
0.000746%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000279%
Overall
0.000125%
2/1,603,984 alleles · very rare
exomes 2/1,452,548 · genomes 0/151,436 · joint denominator
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.Ala1578Ser
- Coding
- c.4732G>T
- MANE Select
- NM_182706
- dbSNP
- rs1554632692
- Type
- single nucleotide variant
- Location
- chr8:143791704 (GRCh38)
- Gene constraint
- LOEUF 0.684 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.33 · 42 PDB
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-ala1578ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown