Is CSTB p.Gln22= (c.66G>A) pathogenic?

CSTB p.Gln22= (c.66G>A) is classified Likely pathogenic in CSTB (ClinVar, No assertion criteria, 2 submitters). Absent from gnomAD v4.1; Associated with Unverricht-Lundborg syndrome.

What condition is associated with CSTB p.Gln22= (c.66G>A)?

CSTB p.Gln22= (c.66G>A) is associated with Unverricht-Lundborg syndrome (ClinVar).

How common is CSTB p.Gln22= (c.66G>A) in the general population?

CSTB p.Gln22= (c.66G>A) is absent from gnomAD v4.1 (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.Gln22=

c.66G>A · rs386833443 · VCV55961

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,531,738)

Conditions

Unverricht-Lundborg syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.45	donor gain · deltas
Pangolin	Δ0.53	loss · gain 0.09 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 6.7	GERP 0.97, phastCons 1
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,531,738). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CSTB
Protein: p.Gln22=
Coding: c.66G>A
MANE Select: NM_000100
dbSNP: rs386833443
Type: single nucleotide variant
Location: chr21:43776204 (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 22: 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 p.Gln22Ter Pathogenic/Likely pathogenic ★★ same residue
CSTB c.67-1G>C Pathogenic ★★ same condition
CSTB p.Arg68Ter 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-gln22 (accessed [today's date]).

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