SETX c.388+69A>C
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.89%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +69 | deep intronic (+69 nt into the intron) |
|---|---|---|
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP 0.88 |
| Non-coding constraint | Z -0.87 | 1 kb window · o/e 1.07 · regional · uncalibrated |
| Overall | ||
| CADD | 1.404 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.89%
South Asian · 3,180/81,778 alleles
Filtering AF
3.78%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.73%
Overall
1.96%
25,239/1,285,578 alleles · low-frequency
exomes 21,915/1,133,284 · genomes 3,324/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 3.89% | 26 |
| Ashkenazi Jewishnot grpmax-eligible | 3.41% | 29 |
| Finnishnot grpmax-eligible | 3.13% | 32 |
| African / African-American | 2.7% | 37 |
| Middle Eastern | 2.61% | 38 |
| Remaining individualsnot grpmax-eligible | 2.1% | 48 |
| European (non-Finnish) | 1.71% | 59 |
| Amishnot grpmax-eligible | 1.43% | 70 |
| East Asian | 1.2% | 83 |
| Admixed American | 0.777% | 129 |
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
- SETX
- Coding
- c.388+69A>C
- MANE Select
- NM_015046
- dbSNP
- rs57353091
- Type
- single nucleotide variant
- Location
- chr9:132346192 (GRCh38)
- Gene constraint
- LOEUF 0.442 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 52.93
Similar variants
- SETX p.Arg111Ter Pathogenic ★★ same type
- SETX p.Arg1363Ter Pathogenic ★★ same type
- SETX p.Arg1606Ter Pathogenic ★★ same type
- SETX p.Arg1778Ter Pathogenic/Likely pathogenic ★★ same type
- SETX p.Arg2098Ter Pathogenic ★★ same type
- SETX p.Arg332Trp Pathogenic/Likely pathogenic ★★ same type
- SETX p.Arg778Ter Pathogenic/Likely pathogenic ★★ same type
- SETX p.Gln1695Ter Pathogenic/Likely pathogenic ★★ 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/setx-c-388-plus-69a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown