Is CSTB p.Arg68Pro (c.203G>C) pathogenic?

CSTB p.Arg68Pro (c.203G>C) is classified Uncertain significance in CSTB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.9251); Absent from gnomAD v4.1; Associated with progressive myoclonus epilepsy.

What condition is associated with CSTB p.Arg68Pro (c.203G>C)?

CSTB p.Arg68Pro (c.203G>C) is associated with progressive myoclonus epilepsy (ClinVar).

How common is CSTB p.Arg68Pro (c.203G>C) in the general population?

CSTB p.Arg68Pro (c.203G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSTB p.Arg68Pro (c.203G>C)?

AlphaMissense predicts likely pathogenic (score 0.9251) — an in-silico prediction, not a clinical call.

CSTB p.Arg68Pro

c.203G>C · rs757707761 · VCV531794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
AlphaMissense	0.9251	likely pathogenic · top 1% in CSTB
REVEL	0.274	benign-leaning
SaProt	LLR -16.85	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.018	GERP -2
Regional constraint	o/e 0.98	unconstrained · MANE · 2,064 bp · p 0.83 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSTB
Protein: p.Arg68Pro
Coding: c.203G>C
MANE Select: NM_000100
dbSNP: rs757707761
Type: single nucleotide variant
Location: chr21:43774296 (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

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

Similar variants

CSTB p.Arg68Ter Pathogenic ★★ 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-arg68pro (accessed [today's date]).

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