CISD2 p.Arg100=
c.300G>A · rs750923436 · VCV1914913
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.022%, 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 0.96 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 8.401 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.022%
South Asian · 20/91,048 alleles
Filtering AF
0.0145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00164%
24/1,461,640 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.022% | 4,552 |
| European (non-Finnish) | 0.000339% | 294,971 |
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.Arg100=
- Coding
- c.300G>A
- MANE Select
- NM_001008388
- dbSNP
- rs750923436
- Type
- single nucleotide variant
- Location
- chr4:102885412 (GRCh38)
- Gene constraint
- LOEUF 0.437 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 90.19 · 4 PDB
- Residue 100
- a β-strand
Similar variants
- CISD2 p.Arg100Gly Uncertain significance ★ ⚠ same residue
- 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
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-arg100 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown