CST3 p.Ala56=
c.168C>T · rs754114926 · VCV2915642
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00561%, 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 -3.1 | GERP -2.7 |
| Overall | ||
| CADD | 4.983 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00561%
African / African-American · 4/71,338 alleles
Filtering AF
0.00191%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.000935%
13/1,391,060 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00561% | 17,834 |
| Remaining individualsnot grpmax-eligible | 0.00503% | 19,888 |
| European (non-Finnish) | 0.000524% | 190,879 |
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.Ala56=
- Coding
- c.168C>T
- MANE Select
- NM_000099
- dbSNP
- rs754114926
- Type
- single nucleotide variant
- Location
- chr20:23637695 (GRCh38)
- Gene constraint
- LOEUF 1.912 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.56 · 11 PDB
- Residue 56
- an α-helix
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-ala56 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown