SORT1 p.Pro747=
c.2241G>A · rs374355693 · VCV3053467
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.312%, eas)
Conditions
1
SORT1-related disorder
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 -0.28 | GERP -3.4, phastCons 0.11 |
| Overall | ||
| CADD | 10.99 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.312%
East Asian · 139/44,536 alleles
Filtering AF
0.27%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.254%
Overall
0.0212%
340/1,601,218 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.312% | 320 |
| South Asian | 0.0503% | 1,990 |
| Remaining individualsnot grpmax-eligible | 0.0226% | 4,429 |
| African / African-American | 0.0148% | 6,769 |
| Admixed American | 0.0119% | 8,403 |
| European (non-Finnish) | 0.0104% | 9,603 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0068% | 14,705 |
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
- SORT1
- Protein
- p.Pro747=
- Coding
- c.2241G>A
- MANE Select
- NM_002959
- dbSNP
- rs374355693
- Type
- single nucleotide variant
- Location
- chr1:109316859 (GRCh38)
- Gene constraint
- LOEUF 0.553 · pLI 0.83 (gnomAD)
- Structure
- AlphaFold pLDDT 83.27 · 17 PDB
- Residue 747
- an α-helix; the 'interactions with lrpap1 and ngfb' region
Disease context
SORT1-related disorder
Similar variants
- SORT1 p.Pro747Leu Uncertain significance ★ ⚠ same residue
- SORT1 c.544-5A>G Likely benign same condition
- SORT1 p.Ile763= Likely benign same condition
- SORT1 p.Phe198= Benign same condition
- SORT1 p.Pro4= Benign same condition
- SORT1 p.Ser409= Likely benign same condition
- SORT1 p.Ser540= Benign same condition
- SORT1 p.Thr323= Benign same condition
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/sort1-p-pro747 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown