GORAB p.Arg28His
c.83G>A · rs144383104 · VCV284846
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.12%, eas)
Conditions
1
geroderma osteodysplasticum
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.061 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic |
| Overall | ||
| CADD | 20.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.12%
East Asian · 54/44,876 alleles
Filtering AF
0.0946%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0855%
Overall
0.0102%
164/1,614,002 alleles · rare
exomes 132/1,461,810 · genomes 32/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.12% | 831 |
| Remaining individualsnot grpmax-eligible | 0.0544% | 1,838 |
| South Asian | 0.0373% | 2,678 |
| African / African-American | 0.0293% | 3,409 |
| Admixed American | 0.00333% | 29,999 |
| Finnishnot grpmax-eligible | 0.00156% | 64,006 |
| European (non-Finnish) | 0.00144% | 69,411 |
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.Arg28His
- Coding
- c.83G>A
- MANE Select
- NM_152281
- dbSNP
- rs144383104
- Type
- single nucleotide variant
- Location
- chr1:170539231 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.86
- Residue 28
- the 'disordered' region
Similar variants
- GORAB p.Arg28Cys Uncertain significance ★★ same residue
- GORAB p.Arg262Ter Pathogenic/Likely pathogenic ★★ same condition
- GORAB p.Arg35Ter Pathogenic ★★ same condition
- GORAB p.Arg40Ter Pathogenic/Likely pathogenic ★★ same condition
- GORAB p.Gln64Ter Pathogenic ★★ same condition
- GORAB c.-21G>A Uncertain significance ★★ same condition
- GORAB c.-28C>G Uncertain significance ★★ same condition
- GORAB c.-53C>A Uncertain significance ★★ same condition
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-arg28his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown