CCZ1 p.Ile345=
c.1035C>T · rs139249929 · VCV2657293
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.233%, 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 | |
| Overall | ||
| CADD | 2.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.233%
Middle Eastern · 14/5,996 alleles
Filtering AF
0.141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.113%
Overall
0.0934%
1,499/1,604,846 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.233% | 428 |
| European (non-Finnish) | 0.117% | 854 |
| Amishnot grpmax-eligible | 0.111% | 904 |
| Remaining individualsnot grpmax-eligible | 0.0901% | 1,110 |
| Admixed American | 0.0254% | 3,938 |
| African / African-American | 0.023% | 4,341 |
| Finnishnot grpmax-eligible | 0.019% | 5,273 |
| South Asian | 0.00989% | 10,108 |
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
- CCZ1
- Protein
- p.Ile345=
- Coding
- c.1035C>T
- MANE Select
- NM_015622
- dbSNP
- rs139249929
- Type
- single nucleotide variant
- Location
- chr7:5919895 (GRCh38)
- Gene constraint
- LOEUF 0.675 · pLI 0.20 (gnomAD)
- Structure
- AlphaFold pLDDT 89.12 · 1 PDB
- Residue 345
- an α-helix
Similar variants
- CCZ1 p.Ala224Ser Uncertain significance ★ same type
- CCZ1 p.Ala224Val Uncertain significance ★ same type
- CCZ1 p.Ala4Val Uncertain significance ★ same type
- CCZ1 p.Arg174Gln Uncertain significance ★ same type
- CCZ1 p.Arg174Trp Uncertain significance ★ same type
- CCZ1 p.Arg269Lys Uncertain significance ★ same type
- CCZ1 p.Arg340Gln Uncertain significance ★ same type
- CCZ1 p.Arg446Trp 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/ccz1-p-ile345 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown