GORAB p.Ala278=
c.834C>T · rs550672557 · VCV1948520
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.022%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.7 | GERP -3.7 |
| Overall | ||
| CADD | 5.902 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.022%
South Asian · 20/91,072 alleles
Filtering AF
0.0145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00235%
38/1,613,966 alleles · ultra-rare
exomes 35/1,461,800 · genomes 3/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.022% | 4,554 |
| East Asian | 0.00668% | 14,960 |
| Admixed American | 0.005% | 19,996 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,833 |
| European (non-Finnish) | 0.000763% | 131,109 |
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.Ala278=
- Coding
- c.834C>T
- MANE Select
- NM_152281
- dbSNP
- rs550672557
- Type
- single nucleotide variant
- Location
- chr1:170552186 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.86
- Residue 278
- the 'necessary for interaction with rchy1' region
Similar variants
- 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
- GORAB p.Trp5Ter Pathogenic/Likely pathogenic ★★ same type
- GORAB c.-21G>A Uncertain significance ★★ same type
- GORAB c.-28C>G 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/gorab-p-ala278 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown