Is HEXB p.Ser80= (c.240C>T) pathogenic?

HEXB p.Ser80= (c.240C>T) is classified Likely benign in HEXB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-12). Absent from gnomAD v4.1; Associated with Sandhoff disease.

What condition is associated with HEXB p.Ser80= (c.240C>T)?

HEXB p.Ser80= (c.240C>T) is associated with Sandhoff disease (ClinVar).

How common is HEXB p.Ser80= (c.240C>T) in the general population?

HEXB p.Ser80= (c.240C>T) is absent from gnomAD v4.1 (gnomAD).

How is Sandhoff disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

HEXB p.Ser80=

c.240C>T · rs2112123022 · VCV1132606

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 -1.4	GERP -3.2
Overall
CADD	8.798	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.Ser80=
Coding: c.240C>T
MANE Select: NM_000521
dbSNP: rs2112123022
Type: single nucleotide variant
Location: chr5:74685500 (GRCh38)
Gene constraint: LOEUF 1.095 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.12 · 8 PDB
Residue 80: a β-strand

Full HEXB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Sandhoff disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sandhoff disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 100 000 (Portugal)

Similar variants

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
HEXB c.445+1G>A 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-ser80 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown