GORAB p.Arg223Gln
c.668G>A · rs564838793 · VCV1916991
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0033%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.3 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 10 | GERP 2, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0033%
South Asian · 3/90,976 alleles
Filtering AF
0.00172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00149%
Overall
0.00211%
34/1,613,596 alleles · very rare
exomes 31/1,461,318 · genomes 3/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0033% | 30,325 |
| European (non-Finnish) | 0.00246% | 40,679 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00133% | 75,028 |
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
- GORAB
- Protein
- p.Arg223Gln
- Coding
- c.668G>A
- MANE Select
- NM_152281
- dbSNP
- rs564838793
- Type
- single nucleotide variant
- Location
- chr1:170552020 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.86
- Residue 223
- the 'necessary for interaction with rchy1' region
Similar variants
- GORAB p.Arg223Pro Uncertain significance ★★ same residue
- GORAB p.Arg223Trp Uncertain significance ★ same residue
- GORAB p.Arg223= Likely benign ★ same residue
- GORAB c.420-2A>T Pathogenic/Likely pathogenic ★★ same type
- GORAB p.Arg262Ter Pathogenic/Likely pathogenic ★★ same type
- GORAB p.Arg35Ter Pathogenic ★★ same type
- GORAB p.Arg40Ter Pathogenic/Likely pathogenic ★★ same type
- GORAB p.Gln64Ter Pathogenic ★★ 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/gorab-p-arg223gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown