Is CSTB p.Ala5= (c.15G>T) pathogenic?

CSTB p.Ala5= (c.15G>T) is classified Benign/Likely benign in CSTB (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Common (popmax 5.55%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CSTB p.Ala5= (c.15G>T)?

CSTB p.Ala5= (c.15G>T) is associated with Inborn genetic diseases, Unverricht-Lundborg syndrome, progressive myoclonus epilepsy (ClinVar).

CSTB p.Ala5=

Q: How common is CSTB p.Ala5= (c.15G>T) in the general population?

CSTB p.Ala5= (c.15G>T) is common (popmax 5.55%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.15G>T · rs4533 · VCV128858

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 5.55%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

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 -0.61	GERP -1.5
Overall
CADD	8.301	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.55% African / African-American · 3,935/70,882 alleles

Filtering AF 5.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.35%

Overall 0.324% 4,956/1,528,018 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.55%	18
Middle Eastern	0.735%	136
Admixed American	0.65%	154
Remaining individualsnot grpmax-eligible	0.507%	197
European (non-Finnish)	0.0296%	3,373
South Asian	0.0195%	5,139

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.Ala5=
Coding: c.15G>T
MANE Select: NM_000100
dbSNP: rs4533
Type: single nucleotide variant
Location: chr21:43776255 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Unverricht-Lundborg syndrome progressive myoclonus epilepsy

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-ala5 (accessed [today's date]).

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