ISCU p.Ser20=
c.60C>T · VCV4765463
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00272%, 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 -1.5 | GERP -4.3 |
| Overall | ||
| CADD | 10.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00272%
South Asian · 2/73,598 alleles
Filtering AF
0.000451%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000169%
Overall
0.000748%
11/1,469,640 alleles · very rare
exomes 9/1,317,308 · genomes 2/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00272% | 36,799 |
| Admixed American | 0.00243% | 41,196 |
| Remaining individualsnot grpmax-eligible | 0.00176% | 56,806 |
| African / African-American | 0.00147% | 68,170 |
| European (non-Finnish) | 0.000536% | 186,656 |
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.Ser20=
- Coding
- c.60C>T
- MANE Select
- NM_213595
- Type
- single nucleotide variant
- Location
- chr12:108562682 (GRCh38)
- Gene constraint
- LOEUF 1.542 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.17 · 18 PDB
Similar variants
- ISCU p.Ser20Asn Uncertain significance ★ ⚠ same residue
- ISCU p.Ser20Ile Uncertain significance ★ ⚠ same residue
- ISCU c.418+382G>C Pathogenic ★★ same type
- ISCU p.Ala105Gly Uncertain significance ★★ ⚠ same type
- ISCU p.Ala13Val 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
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-ser20 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown