SI c.2004+7G>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0292%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +7 | near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3 | GERP -1.7 |
| Non-coding constraint | Z -1.55 | 1 kb window · o/e 1.12 · regional · uncalibrated |
| Overall | ||
| CADD | 0.811 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0292%
South Asian · 26/88,950 alleles
Filtering AF
0.0205%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0175%
Overall
0.00206%
31/1,504,732 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0292% | 3,421 |
| Remaining individualsnot grpmax-eligible | 0.0034% | 29,406 |
| European (non-Finnish) | 0.000278% | 360,288 |
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
- SI
- Coding
- c.2004+7G>A
- MANE Select
- NM_001041
- Type
- single nucleotide variant
- Location
- chr3:165043052 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.86 · 2 PDB
Similar variants
- SI c.2426+1G>A Likely pathogenic ★★ same type
- SI c.2737-2A>G Likely pathogenic ★★ same type
- SI c.2893-1G>A Likely pathogenic ★★ same type
- SI c.3099+1G>C Likely pathogenic ★★ same type
- SI c.3521-1G>T Likely pathogenic ★★ same type
- SI c.373+1G>A Likely pathogenic ★★ same type
- SI c.4575+2T>C Likely pathogenic ★★ same type
- SI c.4927-1G>A 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/si-c-2004-plus-7g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown