CASZ1 p.Pro1111=
c.3333C>T · VCV3625422
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0385%, sas)
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 7.4 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 15.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0385%
South Asian · 35/90,826 alleles
Filtering AF
0.0284%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.025%
Overall
0.00267%
43/1,610,200 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0385% | 2,595 |
| Middle Eastern | 0.0166% | 6,034 |
| East Asian | 0.00223% | 44,786 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,368 |
| European (non-Finnish) | 0.000425% | 235,559 |
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.Pro1111=
- Coding
- c.3333C>T
- MANE Select
- NM_001079843
- Type
- single nucleotide variant
- Location
- chr1:10647965 (GRCh38)
- Gene constraint
- LOEUF 0.285 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.66
- Residue 1111
- 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-pro1111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown