SCLY p.Ala387=
c.1161G>C · rs139057106 · VCV716841
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0746%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.009 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -6.7 | GERP -3.1 |
| Overall | ||
| CADD | 0.255 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0746%
African / African-American · 56/75,048 alleles
Filtering AF
0.0589%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0533%
Overall
0.00385%
62/1,612,132 alleles · ultra-rare
exomes 23/1,459,762 · genomes 39/152,370 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0746% | 1,340 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,783 |
| Admixed American | 0.00334% | 29,905 |
| European (non-Finnish) | 8.48e-05% | 1,179,421 |
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
- SCLY
- Protein
- p.Ala387=
- Coding
- c.1161G>C
- MANE Select
- NM_016510
- dbSNP
- rs139057106
- Type
- single nucleotide variant
- Location
- chr2:238096853 (GRCh38)
- Gene constraint
- LOEUF 1.044 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.14 · 2 PDB
- Residue 387
- an α-helix
Similar variants
- SCLY c.612+7C>T Benign ★★ same type
- SCLY p.Ile86Met Benign ★★ same type
- SCLY p.Phe276Ser Benign ★★ same type
- SCLY p.Val326Ile Benign ★★ same type
- SCLY p.Ala161Gly Uncertain significance ★ ⚠ same type
- SCLY p.Ala183Val Uncertain significance ★ ⚠ same type
- SCLY p.Ala235Ser Uncertain significance ★ ⚠ same type
- SCLY p.Ala267Thr Uncertain significance ★ ⚠ 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/scly-p-ala387 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown