HEXB p.Ser49=
c.147G>C · rs1166509739 · VCV2416691
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Sandhoff disease
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 -2.1 | GERP -3 |
| Overall | ||
| CADD | 2.425 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- HEXB
- Protein
- p.Ser49=
- Coding
- c.147G>C
- MANE Select
- NM_000521
- dbSNP
- rs1166509739
- Type
- single nucleotide variant
- Location
- chr5:74685407 (GRCh38)
- Gene constraint
- LOEUF 1.095 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.12 · 8 PDB
Disease context
Sandhoff disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Sandhoff disease (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Childhood, Infancy
- Prevalence
- 1-9 / 100 000 (Portugal)
Similar variants
- HEXB p.Ser49Ter Pathogenic ★★ same residue
- HEXB c.1082+2T>C Likely pathogenic ★★ same condition
- HEXB c.1082+5G>A Pathogenic/Likely pathogenic ★★ same condition
- HEXB c.1243-2A>G Pathogenic/Likely pathogenic ★★ same condition
- HEXB c.1417+5G>A Pathogenic/Likely pathogenic ★★ same condition
- HEXB c.1508+1G>A Likely pathogenic ★★ same condition
- HEXB c.1509-26G>A Pathogenic/Likely pathogenic ★★ same condition
- HEXB c.300-1G>A Likely pathogenic ★★ 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/hexb-p-ser49 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown