CST3 p.Pro4=
c.12C>T · rs1055084 · VCV1622251
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 8.02%, mid) — too common for a highly-penetrant pathogenic allele
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 -1.3 | GERP -2.4 |
| Overall | ||
| CADD | 5.049 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.02%
Middle Eastern · 314/3,916 alleles
Filtering AF
7.85%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.83%
Overall
6.81%
96,897/1,423,864 alleles · common
exomes 89,780/1,271,634 · genomes 7,117/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 8.02% | 12 |
| European (non-Finnish) | 7.9% | 13 |
| Remaining individualsnot grpmax-eligible | 6.09% | 16 |
| Admixed American | 5.51% | 18 |
| Amishnot grpmax-eligible | 5.04% | 20 |
| Ashkenazi Jewishnot grpmax-eligible | 4.05% | 25 |
| Finnishnot grpmax-eligible | 2.86% | 35 |
| South Asian | 2.7% | 37 |
| African / African-American | 1.28% | 78 |
| East Asian | 0.00582% | 17,195 |
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.Pro4=
- Coding
- c.12C>T
- MANE Select
- NM_000099
- dbSNP
- rs1055084
- Type
- single nucleotide variant
- Location
- chr20:23637851 (GRCh38)
- Gene constraint
- LOEUF 1.912 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.56 · 11 PDB
Similar variants
- CST3 p.Pro4Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown