ULK3 p.Leu99=
c.295C>T · rs188373666 · VCV2645549
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.228%, sas)
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 6.7 | GERP -1, phastCons 1 |
| Overall | ||
| CADD | 10.91 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.228%
South Asian · 208/91,086 alleles
Filtering AF
0.203%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.193%
Overall
0.0668%
1,078/1,613,990 alleles · rare
exomes 982/1,461,670 · genomes 96/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.228% | 438 |
| Middle Eastern | 0.066% | 1,516 |
| European (non-Finnish) | 0.0653% | 1,530 |
| Remaining individualsnot grpmax-eligible | 0.0624% | 1,602 |
| Finnishnot grpmax-eligible | 0.0563% | 1,778 |
| Admixed American | 0.0167% | 6,003 |
| African / African-American | 0.0133% | 7,504 |
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
- ULK3
- Protein
- p.Leu99=
- Coding
- c.295C>T
- MANE Select
- NM_001099436
- dbSNP
- rs188373666
- Type
- single nucleotide variant
- Location
- chr15:74842144 (GRCh38)
- Gene constraint
- LOEUF 1.161 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.96 · 3 PDB
- Residue 99
- the protein kinase domain; an α-helix
Similar variants
- ULK3 p.Arg101His Benign ★★ same type
- ULK3 p.Pro177= Benign ★★ same type
- ULK3 p.Ser468= Benign ★★ same type
- ULK3 p.Ala114Val Uncertain significance ★ ⚠ same type
- ULK3 p.Ala192Thr Uncertain significance ★ ⚠ same type
- ULK3 p.Ala26Thr Uncertain significance ★ ⚠ same type
- ULK3 p.Ala286Val Uncertain significance ★ ⚠ same type
- ULK3 p.Ala303Thr Uncertain significance ★ ⚠ 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/ulk3-p-leu99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown