CISD2 p.Leu48=
c.144C>T · rs371712100 · VCV2188144
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.096 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -3.9 |
| Overall | ||
| CADD | 7.746 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/74,904 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00204%
33/1,613,928 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,567 |
| Admixed American | 0.00167% | 59,990 |
| European (non-Finnish) | 0.000932% | 107,271 |
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.Leu48=
- Coding
- c.144C>T
- MANE Select
- NM_001008388
- dbSNP
- rs371712100
- Type
- single nucleotide variant
- Location
- chr4:102885256 (GRCh38)
- Gene constraint
- LOEUF 0.437 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 90.19 · 4 PDB
Similar variants
- CISD2 p.Leu48Phe 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-leu48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown