CISD2 p.Tyr98=
c.294T>C · rs151223492 · VCV745094
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.121%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.29 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.77 | GERP -1.8, phastCons 0.019 |
| Overall | ||
| CADD | 4.779 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.121%
African / African-American · 91/75,056 alleles
Filtering AF
0.101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0936%
Overall
0.00626%
101/1,614,000 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.121% | 825 |
| Admixed American | 0.00833% | 12,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,833 |
| European (non-Finnish) | 0.00017% | 589,960 |
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
- CISD2
- Protein
- p.Tyr98=
- Coding
- c.294T>C
- MANE Select
- NM_001008388
- dbSNP
- rs151223492
- Type
- single nucleotide variant
- Location
- chr4:102885406 (GRCh38)
- Gene constraint
- LOEUF 0.437 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 90.19 · 4 PDB
- Residue 98
- a β-strand
Similar variants
- CISD2 c.103+6C>A Uncertain significance ★★ same type
- CISD2 p.Arg57Cys Uncertain significance ★★ ⚠ same type
- CISD2 p.Arg57His Uncertain significance ★★ ⚠ same type
- CISD2 p.Asn87Ser Uncertain significance ★★ ⚠ same type
- CISD2 p.Glu4Gln Uncertain significance ★★ ⚠ same type
- CISD2 p.Pro61Leu Uncertain significance ★★ ⚠ same type
- CISD2 p.Pro80Leu Uncertain significance ★★ ⚠ same type
- CISD2 p.Thr28Ile 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/cisd2-p-tyr98 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown