Is CSTB p.Glu15= (c.45G>A) pathogenic?

CSTB p.Glu15= (c.45G>A) is classified Conflicting classifications of pathogenicity in CSTB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-02-04). Rare (popmax 0.523%, eas); Associated with progressive myoclonus epilepsy.

What condition is associated with CSTB p.Glu15= (c.45G>A)?

CSTB p.Glu15= (c.45G>A) is associated with progressive myoclonus epilepsy, Unverricht-Lundborg syndrome (ClinVar).

How common is CSTB p.Glu15= (c.45G>A) in the general population?

CSTB p.Glu15= (c.45G>A) is rare (popmax 0.523%, eas) (gnomAD).

CSTB p.Glu15=

c.45G>A · rs1057521317 · VCV382295

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.523%, eas)

Conditions

progressive myoclonus epilepsy

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 -0.51	GERP -0.23, phastCons 0.01
Overall
CADD	11.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.523% East Asian · 210/40,130 alleles

Filtering AF 0.465% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.443%

Overall 0.0143% 219/1,532,286 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.523%	191
Remaining individualsnot grpmax-eligible	0.00503%	19,866
Admixed American	0.00396%	25,237
European (non-Finnish)	0.00035%	285,689

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.Glu15=
Coding: c.45G>A
MANE Select: NM_000100
dbSNP: rs1057521317
Type: single nucleotide variant
Location: chr21:43776225 (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 15: an α-helix

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

Disease context

progressive myoclonus epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Unverricht-Lundborg syndrome

Similar variants

CSTB p.Glu15Ter Likely pathogenic ★ same residue
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.Ala49Thr Uncertain significance ★★ same condition
CSTB p.Ala90Thr Uncertain significance ★★ ⚠ same condition
CSTB p.Asn52Ile Uncertain significance ★★ ⚠ 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-glu15 (accessed [today's date]).

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