CIROZ p.Val232Ala
c.695T>C · rs202029856 · VCV2215940
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0137%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.112 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor loss · deltas |
| Pangolin | Δ0.21 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 0.6, phastCons 0.01 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 34 kb · p 0.059 · regional, not allelic |
| Overall | ||
| CADD | 13.45 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0137%
European (non-Finnish) · 157/1,146,436 alleles
Filtering AF
0.0119%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0112%
Overall
0.0107%
166/1,548,738 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0137% | 7,302 |
| Remaining individualsnot grpmax-eligible | 0.0134% | 7,487 |
| Finnishnot grpmax-eligible | 0.00167% | 59,756 |
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
- CIROZ
- Protein
- p.Val232Ala
- Coding
- c.695T>C
- MANE Select
- NM_001170754
- dbSNP
- rs202029856
- Type
- single nucleotide variant
- Location
- chr1:10957106 (GRCh38)
- Structure
- AlphaFold pLDDT 53.62
- Residue 232
- a UniProt-annotated variant site (in htx14; pathogenic)
Similar variants
- CIROZ p.Gly689Arg Benign ★★ same type
- CIROZ p.Arg732Ter Likely pathogenic ★ same type
- CIROZ p.Tyr128Ter Likely pathogenic ★ same type
- CIROZ p.Ala750Val Uncertain significance ★ same type
- CIROZ p.Arg113Ter Conflicting classifications of pathogenicity ★ same type
- CIROZ p.Gln263Lys Uncertain significance ★ same type
- CIROZ p.Gly629Val Uncertain significance ★ same type
- CIROZ p.Leu771Ile 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/ciroz-p-val232ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown