Is CSTB p.Gln26Ter (c.76C>T) pathogenic?

CSTB p.Gln26Ter (c.76C>T) is classified Likely pathogenic in CSTB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-19). Very rare (popmax 0.00133%, afr); Associated with Unverricht-Lundborg syndrome.

What condition is associated with CSTB p.Gln26Ter (c.76C>T)?

CSTB p.Gln26Ter (c.76C>T) is associated with Unverricht-Lundborg syndrome (ClinVar).

How common is CSTB p.Gln26Ter (c.76C>T) in the general population?

CSTB p.Gln26Ter (c.76C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Progressive myoclonic epilepsy type 1 inherited?

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

CSTB p.Gln26Ter

c.76C>T · VCV3376548

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Unverricht-Lundborg syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.53, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,018 alleles

Overall 6.84e-05% 1/1,461,492 alleles · very rare

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: CSTB
Protein: p.Gln26Ter
Coding: c.76C>T
MANE Select: NM_000100
Type: single nucleotide variant
Location: chr21:43774750 (GRCh38)
Gene constraint: LOEUF 1.681 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.81 · 3 PDB
Residue 26: an α-helix

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

Disease context

Unverricht-Lundborg syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive myoclonic epilepsy type 1 (Orphanet):

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

Similar variants

CSTB c.67-1G>C Pathogenic ★★ same condition
CSTB p.Arg68Ter Pathogenic ★★ same condition
CSTB p.Gln22Ter Pathogenic/Likely pathogenic ★★ same condition
CSTB p.Gln46Ter Pathogenic/Likely pathogenic ★★ same condition
CSTB p.Tyr53Cys Uncertain significance ★★ ⚠ same condition
CSTB p.Val57Leu Uncertain significance ★★ ⚠ same condition
CSTB c.67-3T>C Benign/Likely benign ★★ same condition
CSTB c.-54C>T Benign ★★ 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/cstb-p-gln26ter (accessed [today's date]).

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