CIROZ p.Arg418Gln
c.1253G>A · rs534520725 · VCV2235445
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00845%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.017 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.1 | GERP -2.7 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 34 kb · p 0.059 · regional, not allelic |
| Overall | ||
| CADD | 0.097 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00845%
Admixed American · 5/59,174 alleles
Filtering AF
0.00327%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00209%
Overall
0.000933%
15/1,607,288 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00845% | 11,835 |
| African / African-American | 0.00401% | 24,960 |
| South Asian | 0.00224% | 44,700 |
| European (non-Finnish) | 0.000425% | 235,457 |
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.Arg418Gln
- Coding
- c.1253G>A
- MANE Select
- NM_001170754
- dbSNP
- rs534520725
- Type
- single nucleotide variant
- Location
- chr1:10949661 (GRCh38)
- Structure
- AlphaFold pLDDT 53.62
- Residue 418
- 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-arg418gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown