Is CST3 c.357+1del pathogenic?

CST3 c.357+1del is classified Uncertain significance in CST3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-08-05). Absent from gnomAD; Associated with CST3-related Leukodystrophy.

What condition is associated with CST3 c.357+1del?

CST3 c.357+1del is associated with CST3-related Leukodystrophy, leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathy (ClinVar).

How common is CST3 c.357+1del in the general population?

CST3 c.357+1del is absent from gnomAD (gnomAD).

CST3 c.357+1del

rs34930898 · VCV1712339

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CST3-related Leukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 10	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CST3
Coding: c.357+1del
MANE Select: NM_000099
dbSNP: rs34930898
Type: Deletion
Location: chr20:23635253 (GRCh38)
Gene constraint: LOEUF 1.912 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.56 · 11 PDB

Full CST3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CST3-related Leukodystrophy

Also linked: leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathy

Similar variants

CST3 p.Ala121fs Uncertain significance ★ same condition
CST3 p.Gln114Ter Conflicting classifications of pathogenicity ★ same condition
CST3 p.Gly26Cys Likely benign ★ same condition
CST3 c.226_243+3del Uncertain significance ★ same type
CST3 p.Asp66del Uncertain significance ★ same type
CST3 p.Gln114fs Uncertain significance ★ same type
CST3 p.Phe122fs Uncertain significance ★ same type

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/cst3-c-357-plus-1del (accessed [today's date]).

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