Is CSTB p.Arg68Ter (c.202C>T) pathogenic?

CSTB p.Arg68Ter (c.202C>T) is classified Pathogenic in CSTB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-06-19). Very rare (popmax 0.00593%, nfe); Associated with CSTB-related disorder.

What condition is associated with CSTB p.Arg68Ter (c.202C>T)?

CSTB p.Arg68Ter (c.202C>T) is associated with CSTB-related disorder, dystonic disorder, self-limited epilepsy with centrotemporal spikes (ClinVar).

How common is CSTB p.Arg68Ter (c.202C>T) in the general population?

CSTB p.Arg68Ter (c.202C>T) is very rare (popmax 0.00593%, nfe) (gnomAD).

CSTB p.Arg68Ter

c.202C>T · rs74315442 · VCV8396

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Conditions

CSTB-related disorder

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	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.70	gain · loss 0.14 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2	GERP -4.4, phastCons 0.021
Overall
CADD	36.0	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 0.00593% European (non-Finnish) · 70/1,180,050 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00465% 75/1,614,088 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00593%	16,858
Remaining individualsnot grpmax-eligible	0.0032%	31,240
East Asian	0.00223%	44,902
Finnishnot grpmax-eligible	0.00156%	64,006
African / African-American	0.00133%	74,946

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.Arg68Ter
Coding: c.202C>T
MANE Select: NM_000100
dbSNP: rs74315442
Type: single nucleotide variant
Location: chr21:43774297 (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 68: a β-strand

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

Disease context

CSTB-related disorder

Also linked: dystonic disorder self-limited epilepsy with centrotemporal spikes Unverricht-Lundborg syndrome progressive myoclonus epilepsy

Similar variants

CSTB p.Arg68Pro Uncertain significance ★ ⚠ same residue
CSTB c.67-1G>C 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
CSTB p.Gln10Glu 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-arg68ter (accessed [today's date]).

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