Is CSTB p.Gln71Pro (c.212A>C) pathogenic?

CSTB p.Gln71Pro (c.212A>C) is classified Pathogenic in CSTB (ClinVar, No assertion criteria, 2 submitters; last evaluated 2005-02-01). AlphaMissense: likely pathogenic (0.571); Absent from gnomAD v4.1; Associated with Unverricht-Lundborg syndrome.

What condition is associated with CSTB p.Gln71Pro (c.212A>C)?

CSTB p.Gln71Pro (c.212A>C) is associated with Unverricht-Lundborg syndrome (ClinVar).

How common is CSTB p.Gln71Pro (c.212A>C) in the general population?

CSTB p.Gln71Pro (c.212A>C) 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.

What do computational predictors say about CSTB p.Gln71Pro (c.212A>C)?

AlphaMissense predicts likely pathogenic (score 0.571) — an in-silico prediction, not a clinical call.

CSTB p.Gln71Pro

c.212A>C · rs121909346 · VCV8400

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.571 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Unverricht-Lundborg syndrome

Computational evidence

Protein change
AlphaMissense	0.571	likely pathogenic ✓ concordant with ClinVar
REVEL	0.484	indeterminate
SaProt	LLR -15.00	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.55	GERP -3.3
Regional constraint	o/e 0.98	unconstrained · MANE · 2,064 bp · p 0.83 · regional, not allelic
Overall
CADD	11.4	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.Gln71Pro
Coding: c.212A>C
MANE Select: NM_000100
dbSNP: rs121909346
Type: single nucleotide variant
Location: chr21:43774287 (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 71: a β-strand

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.Gln71= Likely benign ★ 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.Tyr53Cys Uncertain significance ★★ ⚠ same condition
CSTB p.Val57Leu Uncertain significance ★★ ⚠ same condition
CSTB c.67-3T>C Benign/Likely 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-gln71pro (accessed [today's date]).

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