LIG1 p.Pro599=
c.1797G>A · rs368088071 · VCV1917604
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0446%, eas)
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 -20 | GERP -3.1 |
| Overall | ||
| CADD | 1.773 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0446%
East Asian · 20/44,886 alleles
Filtering AF
0.0295%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0246%
Overall
0.00223%
36/1,613,974 alleles · ultra-rare
exomes 35/1,461,794 · genomes 1/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0446% | 2,244 |
| Admixed American | 0.005% | 20,001 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,240 |
| South Asian | 0.0011% | 91,090 |
| European (non-Finnish) | 0.000847% | 117,996 |
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
- LIG1
- Protein
- p.Pro599=
- Coding
- c.1797G>A
- MANE Select
- NM_000234
- dbSNP
- rs368088071
- Type
- single nucleotide variant
- Location
- chr19:48131100 (GRCh38)
- Structure
- AlphaFold pLDDT 75.13 · 2 PDB
- Residue 599
- a β-strand; the ig-like c2-type 2 domain
Similar variants
- LIG1 p.Pro599Leu Uncertain significance ★ ⚠ same residue
- LRIG1 p.Pro599= Likely benign ★ same residue
- LIG1 p.Ala269Thr Uncertain significance ★★ ⚠ same type
- LIG1 p.Ala293Val Uncertain significance ★★ ⚠ same type
- LIG1 p.Ala412Thr Uncertain significance ★★ ⚠ same type
- LIG1 p.Ala443Thr Uncertain significance ★★ ⚠ same type
- LIG1 p.Ala462Ser Uncertain significance ★★ ⚠ same type
- LIG1 p.Ala545Gly 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/lig1-p-pro599 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown