SI p.Arg647=
c.1939A>C · rs781340245 · VCV2993705
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.047%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 11.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.047%
East Asian · 21/44,716 alleles
Filtering AF
0.0314%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0264%
Overall
0.0013%
21/1,612,712 alleles · ultra-rare
exomes 20/1,460,600 · genomes 1/152,112 · joint denominator
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.Arg647=
- Coding
- c.1939A>C
- MANE Select
- NM_001041
- dbSNP
- rs781340245
- Type
- single nucleotide variant
- Location
- chr3:165043124 (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 647
- the 'isomaltase' region; an α-helix
Similar variants
- SI p.Arg647fs Pathogenic ★ 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
- SI c.4575+2T>C 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-arg647 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown