CST3 p.Ser139=
c.417G>A · rs77000936 · VCV728906
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.874%, 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 -2.8 | GERP -2.8 |
| Overall | ||
| CADD | 1.613 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.874%
African / African-American · 656/75,022 alleles
Filtering AF
0.819%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.797%
Overall
0.0463%
747/1,614,106 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.874% | 114 |
| Remaining individualsnot grpmax-eligible | 0.0592% | 1,689 |
| Admixed American | 0.0466% | 2,144 |
| Finnishnot grpmax-eligible | 0.00312% | 32,006 |
| European (non-Finnish) | 0.00195% | 51,305 |
| South Asian | 0.0011% | 91,082 |
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
- CST3
- Protein
- p.Ser139=
- Coding
- c.417G>A
- MANE Select
- NM_000099
- dbSNP
- rs77000936
- Type
- single nucleotide variant
- Location
- chr20:23633940 (GRCh38)
- Gene constraint
- LOEUF 1.912 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.56 · 11 PDB
- Residue 139
- a UniProt-annotated variant site (in adldwa; uncertain significance); a β-strand; a disulfide bond; a UniProt-annotated variant site (in adldwa; likely pathogenic)
Similar variants
- CST3 p.Arg71His Uncertain significance ★★ ⚠ same type
- CST3 p.His112Arg Uncertain significance ★★ ⚠ same type
- CST3 p.Met67Val Uncertain significance ★★ ⚠ same type
- CST3 p.Pro8Ser Uncertain significance ★★ ⚠ same type
- CST3 c.243+11C>T Likely benign ★★ same type
- CST3 p.Ala25Thr Benign/Likely benign ★★ same type
- CST3 p.Ala72Ser Benign ★★ ⚠ same type
- CST3 p.Arg6= Benign/Likely benign ★★ 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/cst3-p-ser139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown