CASZ1 p.Ala1069=
c.3207T>C · rs749934013 · VCV2175344
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0172%, amr)
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 -0.35 | GERP -3.3 |
| Overall | ||
| CADD | 7.473 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0172%
Admixed American · 9/52,474 alleles
Filtering AF
0.00894%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00661%
Overall
0.000701%
11/1,569,848 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0172% | 5,830 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,672 |
| European (non-Finnish) | 8.63e-05% | 1,158,856 |
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
- CASZ1
- Protein
- p.Ala1069=
- Coding
- c.3207T>C
- MANE Select
- NM_001079843
- dbSNP
- rs749934013
- Type
- single nucleotide variant
- Location
- chr1:10648091 (GRCh38)
- Gene constraint
- LOEUF 0.285 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.66
- Residue 1069
- the 'disordered' region
Similar variants
- CASZ1 p.Ala1274Val Uncertain significance ★★ ⚠ same type
- CASZ1 p.Ala1321Val Uncertain significance ★★ ⚠ same type
- CASZ1 p.Ala136Val Uncertain significance ★★ ⚠ same type
- CASZ1 p.Ala155Pro Uncertain significance ★★ ⚠ same type
- CASZ1 p.Ala178Val Uncertain significance ★★ ⚠ same type
- CASZ1 p.Ala22Val Uncertain significance ★★ ⚠ same type
- CASZ1 p.Ala307Thr Uncertain significance ★★ ⚠ same type
- CASZ1 p.Ala978Thr 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/casz1-p-ala1069 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown