ISCU p.Ala13=
c.39A>C · rs533283101 · VCV1194859
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.148%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -5.2 |
| Overall | ||
| CADD | 0.918 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.148%
South Asian · 107/72,154 alleles
Filtering AF
0.126%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.117%
Overall
0.00804%
117/1,454,916 alleles · rare
exomes 110/1,302,682 · genomes 7/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.148% | 674 |
| Remaining individualsnot grpmax-eligible | 0.0142% | 7,037 |
| Admixed American | 0.0024% | 41,604 |
| European (non-Finnish) | 9.01e-05% | 1,109,484 |
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
- ISCU
- Protein
- p.Ala13=
- Coding
- c.39A>C
- MANE Select
- NM_213595
- dbSNP
- rs533283101
- Type
- single nucleotide variant
- Location
- chr12:108562661 (GRCh38)
- Gene constraint
- LOEUF 1.542 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.17 · 18 PDB
Similar variants
- ISCU p.Ala13Val Uncertain significance ★★ ⚠ same residue
- ISCU c.418+382G>C Pathogenic ★★ same type
- ISCU p.Ala105Gly Uncertain significance ★★ ⚠ same type
- ISCU p.Ala149Thr Uncertain significance ★★ ⚠ same type
- ISCU p.Ala15Thr Uncertain significance ★★ ⚠ same type
- ISCU p.Ala30Val Uncertain significance ★★ ⚠ same type
- ISCU p.Ala6Val Uncertain significance ★★ ⚠ same type
- ISCU p.Arg11Pro 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/iscu-p-ala13 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown