CTSA c.1254+8A>G
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000171%, nfe)
Conditions
1
galactosialidosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +8 | near-intronic (+8 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.26 | GERP -1.1 |
| Non-coding constraint | Z 3.61 | 1 kb window · o/e 0.73 · regional · uncalibrated |
| Overall | ||
| CADD | 2.331 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000171%
European (non-Finnish) · 2/1,166,804 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000138%
2/1,447,412 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
- CTSA
- Coding
- c.1254+8A>G
- MANE Select
- NM_000308
- dbSNP
- rs2515447924
- Type
- single nucleotide variant
- Location
- chr20:45897814 (GRCh38)
- Gene constraint
- LOEUF 0.851 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.59 · 12 PDB
Disease context
galactosialidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Galactosialidosis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
Similar variants
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- CTSA c.692+3A>G Pathogenic ★★ same condition
- CTSA c.948+1G>A Likely pathogenic ★★ same condition
- CTSA p.Arg375Ter Pathogenic/Likely pathogenic ★★ same condition
- CTSA p.Cys256Ter Pathogenic/Likely pathogenic ★★ same condition
- CTSA p.Cys281Ter Pathogenic/Likely pathogenic ★★ 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/ctsa-c-1254-plus-8a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown