Is CSTB p.Asp61= (c.183C>T) pathogenic?

CSTB p.Asp61= (c.183C>T) is classified Likely benign in CSTB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-21). Ultra-rare (popmax 0.0173%, afr); Associated with progressive myoclonus epilepsy.

What condition is associated with CSTB p.Asp61= (c.183C>T)?

CSTB p.Asp61= (c.183C>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is CSTB p.Asp61= (c.183C>T) in the general population?

CSTB p.Asp61= (c.183C>T) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

CSTB p.Asp61=

c.183C>T · rs772899788 · VCV386806

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

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 -7.4	GERP -4.1
Overall
CADD	0.244	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% African / African-American · 13/74,942 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00434% 70/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,765
Admixed American	0.00833%	12,002
East Asian	0.00445%	22,452
European (non-Finnish)	0.00398%	25,108
Remaining individualsnot grpmax-eligible	0.0032%	31,244
South Asian	0.0011%	91,088

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.Asp61=
Coding: c.183C>T
MANE Select: NM_000100
dbSNP: rs772899788
Type: single nucleotide variant
Location: chr21:43774316 (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 61: 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 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
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-asp61 (accessed [today's date]).

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