GORAB p.Cys355Phe
c.1064G>T · rs149089833 · VCV875795
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.143%, eas)
Conditions
1
geroderma osteodysplasticum
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.052 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -4.3 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic |
| Overall | ||
| CADD | 0.338 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.143%
East Asian · 64/44,888 alleles
Filtering AF
0.115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.104%
Overall
0.00428%
69/1,614,014 alleles · rare
exomes 58/1,461,726 · genomes 11/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.143% | 701 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| African / African-American | 0.00133% | 75,030 |
| South Asian | 0.0011% | 91,074 |
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.Cys355Phe
- Coding
- c.1064G>T
- MANE Select
- NM_152281
- dbSNP
- rs149089833
- Type
- single nucleotide variant
- Location
- chr1:170552416 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.86
- Residue 355
- the 'necessary for interaction with rchy1' region; the 'disordered' region
Similar variants
- 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
- GORAB p.Ala220Thr 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-cys355phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown