SI p.Ala599=
c.1797G>A · rs9838509 · VCV2063408
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0331%, mid)
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 -4.3 | GERP -3.9 |
| Overall | ||
| CADD | 5.371 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
Middle Eastern · 2/6,048 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.00174%
28/1,612,404 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0331% | 3,024 |
| South Asian | 0.0209% | 4,781 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,219 |
| African / African-American | 0.00267% | 37,458 |
| European (non-Finnish) | 0.000254% | 393,042 |
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
- Protein
- p.Ala599=
- Coding
- c.1797G>A
- MANE Select
- NM_001041
- dbSNP
- rs9838509
- Type
- single nucleotide variant
- Location
- chr3:165046931 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.86 · 2 PDB
- Residue 599
- the 'isomaltase' region; a β-strand
Similar variants
- SI p.Ala599Val Uncertain significance ★★ ⚠ same residue
- SI p.Ala599Ser Uncertain significance ★ ⚠ same residue
- 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
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-p-ala599 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown