Is CSTB p.Cys3= (c.9C>T) pathogenic?

CSTB p.Cys3= (c.9C>T) is classified Conflicting classifications of pathogenicity in CSTB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-20). Ultra-rare (popmax 0.0253%, eas); Associated with progressive myoclonus epilepsy.

What condition is associated with CSTB p.Cys3= (c.9C>T)?

CSTB p.Cys3= (c.9C>T) is associated with progressive myoclonus epilepsy, Unverricht-Lundborg syndrome (ClinVar).

How common is CSTB p.Cys3= (c.9C>T) in the general population?

CSTB p.Cys3= (c.9C>T) is ultra-rare (popmax 0.0253%, eas) (gnomAD).

CSTB p.Cys3=

c.9C>T · rs555930471 · VCV895890

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, 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 0.053	GERP -4.1, phastCons 0.31
Overall
CADD	6.732	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% East Asian · 10/39,506 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0104%

Overall 0.000981% 15/1,528,398 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0253%	3,951
Finnishnot grpmax-eligible	0.00194%	51,624
Remaining individualsnot grpmax-eligible	0.00168%	59,368
African / African-American	0.00141%	70,916
European (non-Finnish)	0.000175%	570,054

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.Cys3=
Coding: c.9C>T
MANE Select: NM_000100
dbSNP: rs555930471
Type: single nucleotide variant
Location: chr21:43776261 (GRCh38)
Gene constraint: LOEUF 1.681 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.81 · 3 PDB

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.Cys3Trp Uncertain significance ★ ⚠ 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-cys3 (accessed [today's date]).

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