ULK1 p.Leu596=
c.1788G>A · rs111386946 · VCV768599
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.79%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.7 | GERP -2.6 |
| Overall | ||
| CADD | 0.198 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.79%
African / African-American · 4,339/74,960 alleles
Filtering AF
5.64%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.59%
Overall
0.302%
4,863/1,612,360 alleles · common
exomes 2,412/1,460,242 · genomes 2,451/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.79% | 17 |
| Remaining individualsnot grpmax-eligible | 0.352% | 284 |
| Admixed American | 0.345% | 290 |
| Middle Eastern | 0.116% | 866 |
| South Asian | 0.00878% | 11,385 |
| European (non-Finnish) | 0.00695% | 14,388 |
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
- ULK1
- Protein
- p.Leu596=
- Coding
- c.1788G>A
- MANE Select
- NM_003565
- dbSNP
- rs111386946
- Type
- single nucleotide variant
- Location
- chr12:131916069 (GRCh38)
- Gene constraint
- LOEUF 0.61 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99 · 19 PDB
- Residue 596
- the 'disordered' region
Similar variants
- ULK1 p.Thr660Met Uncertain significance ★★ ⚠ same type
- ULK1 p.Ala923= Benign ★★ same type
- ULK1 p.Arg966= Benign ★★ same type
- ULK1 p.Gly757= Benign ★★ same type
- ULK1 p.Leu926= Benign ★★ same type
- ULK1 p.Leu957= Benign/Likely benign ★★ same type
- ULK1 p.Pro574= Benign/Likely benign ★★ same type
- ULK1 p.Pro574Arg Likely benign ★★ 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/ulk1-p-leu596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown