SCRIB p.Phe1577Tyr
c.4730T>A · VCV4581377
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0385%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.1 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 1.13 | unconstrained · MANE · 20 kb · p 9.1e-08 · regional, not allelic |
| Overall | ||
| CADD | 25.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0385%
South Asian · 35/90,924 alleles
Filtering AF
0.0284%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0249%
Overall
0.00293%
47/1,604,608 alleles · ultra-rare
exomes 43/1,452,686 · genomes 4/151,922 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0385% | 2,598 |
| Middle Eastern | 0.0165% | 6,054 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 61,982 |
| European (non-Finnish) | 0.000852% | 117,318 |
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.Phe1577Tyr
- Coding
- c.4730T>A
- MANE Select
- NM_182706
- Type
- single nucleotide variant
- Location
- chr8:143791706 (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-phe1577tyr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown