ISCU p.Cys69=
c.207T>C · rs761837713 · VCV1013017
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00144%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.04 | GERP -0.21, phastCons 0.91 |
| Overall | ||
| CADD | 10.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00144%
European (non-Finnish) · 17/1,179,060 alleles
Filtering AF
0.000878%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000718%
Overall
0.00112%
18/1,613,068 alleles · very rare
exomes 16/1,460,810 · genomes 2/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00144% | 69,356 |
| African / African-American | 0.00133% | 74,936 |
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.Cys69=
- Coding
- c.207T>C
- MANE Select
- NM_213595
- dbSNP
- rs761837713
- Type
- single nucleotide variant
- Location
- chr12:108564371 (GRCh38)
- Gene constraint
- LOEUF 1.542 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.17 · 18 PDB
- Residue 69
- an active site; an α-helix; a modified residue (cysteine persulfide)
Similar variants
- 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
- 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-cys69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown