ISCU p.Val72=
c.216A>G · VCV4753655
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0312%, eas)
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 -0.24 | GERP -5.6, phastCons 0.041 |
| Overall | ||
| CADD | 6.086 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0312%
East Asian · 14/44,892 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.000993%
16/1,611,362 alleles · ultra-rare
exomes 10/1,459,102 · genomes 6/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0312% | 3,207 |
| African / African-American | 0.00133% | 74,908 |
| European (non-Finnish) | 8.49e-05% | 1,177,460 |
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.Val72=
- Coding
- c.216A>G
- MANE Select
- NM_213595
- Type
- single nucleotide variant
- Location
- chr12:108564380 (GRCh38)
- Gene constraint
- LOEUF 1.542 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.17 · 18 PDB
- Residue 72
- a β-strand
Similar variants
- ISCU p.Val72Ile 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
- ISCU p.Ala6Val 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-val72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown