Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.91%, afr)
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 -0.45 | GERP -0.64 |
| Overall | ||
| CADD | 7.395 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.91%
African / African-American · 2,935/74,996 alleles
Filtering AF
3.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.75%
Overall
0.218%
3,516/1,614,144 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.91% | 26 |
| Admixed American | 0.44% | 227 |
| Remaining individualsnot grpmax-eligible | 0.342% | 292 |
| Middle Eastern | 0.214% | 466 |
| South Asian | 0.00769% | 13,011 |
| European (non-Finnish) | 0.00703% | 14,217 |
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
- CST4
- Protein
- p.Lys96=
- Coding
- c.288G>A
- MANE Select
- NM_001899
- dbSNP
- rs6048994
- Type
- single nucleotide variant
- Location
- chr20:23687142 (GRCh38)
- Gene constraint
- LOEUF 1.874 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.01
- Residue 96
- a disulfide bond
Similar variants
- CST4 p.Ala141Ser Benign ★★ same type
- CST4 p.Arg3= Benign ★★ same type
- CST4 p.Asn40Ser Benign ★★ same type
- CST4 p.Leu8Gln Benign ★★ ⚠ same type
- CST4 p.Ala16Val Uncertain significance ★ ⚠ same type
- CST4 p.Ala18Gly Uncertain significance ★ ⚠ same type
- CST4 p.Arg91Cys Uncertain significance ★ ⚠ same type
- CST4 p.Arg91His 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/cst4-p-lys96 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown