CST3 p.Asp145=
c.435C>T · VCV3704578
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, mid)
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 -6.4 | GERP -2.8 |
| Overall | ||
| CADD | 0.387 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,080 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00716%
Overall
0.00421%
68/1,613,796 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,027 |
| European (non-Finnish) | 0.00483% | 20,698 |
| Admixed American | 0.00333% | 30,007 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| African / African-American | 0.00267% | 37,457 |
| South Asian | 0.0022% | 45,540 |
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.Asp145=
- Coding
- c.435C>T
- MANE Select
- NM_000099
- Type
- single nucleotide variant
- Location
- chr20:23633922 (GRCh38)
- Gene constraint
- LOEUF 1.912 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.56 · 11 PDB
- Residue 145
- a UniProt-annotated variant site (in adldwa; uncertain significance); a β-strand; 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-asp145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown