Is CSTB p.Ala14= (c.42C>G) pathogenic?

CSTB p.Ala14= (c.42C>G) is classified Likely benign in CSTB (ClinVar, Single submitter, 2 submitters; last evaluated 2020-11-16). Very rare (popmax 0.000438%, nfe); Associated with progressive myoclonus epilepsy.

What condition is associated with CSTB p.Ala14= (c.42C>G)?

CSTB p.Ala14= (c.42C>G) is associated with progressive myoclonus epilepsy (ClinVar).

How common is CSTB p.Ala14= (c.42C>G) in the general population?

CSTB p.Ala14= (c.42C>G) is very rare (popmax 0.000438%, nfe) (gnomAD).

CSTB p.Ala14=

c.42C>G · rs2123387857 · VCV1652345

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000438%, nfe)

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 -0.8	GERP -4.1
Overall
CADD	10.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000438% European (non-Finnish) · 5/1,142,430 alleles

Filtering AF 0.000128% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000362% 5/1,379,358 alleles · very rare

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.Ala14=
Coding: c.42C>G
MANE Select: NM_000100
dbSNP: rs2123387857
Type: single nucleotide variant
Location: chr21:43776228 (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 14: an α-helix

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.Ala14Ser Uncertain significance ★ ⚠ 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.Ala49Thr Uncertain significance ★★ ⚠ same condition
CSTB p.Ala90Thr Uncertain significance ★★ ⚠ same condition
CSTB p.Asn52Ile 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-ala14 (accessed [today's date]).

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