SI p.Leu274=
c.820T>C · rs377210825 · VCV2654261
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0386%, sas)
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 8.1 | GERP -0.64, phastCons 1 |
| Overall | ||
| CADD | 9.452 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0386%
South Asian · 32/82,976 alleles
Filtering AF
0.028%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0244%
Overall
0.00304%
44/1,448,850 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0386% | 2,593 |
| Middle Eastern | 0.0353% | 2,835 |
| Remaining individualsnot grpmax-eligible | 0.00177% | 56,472 |
| European (non-Finnish) | 0.000866% | 115,466 |
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.Leu274=
- Coding
- c.820T>C
- MANE Select
- NM_001041
- dbSNP
- rs377210825
- Type
- single nucleotide variant
- Location
- chr3:165063529 (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 274
- the 'isomaltase' region
Similar variants
- SI p.Leu274Phe 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
- 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-leu274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown