LIG1 p.Arg440=
c.1320G>A · rs766768659 · VCV1560947
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0212%, nfe)
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 -3.7 | GERP -3.3 |
| Overall | ||
| CADD | 0.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0212%
European (non-Finnish) · 250/1,179,456 alleles
Filtering AF
0.019%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0182%
Overall
0.0161%
259/1,612,526 alleles · ultra-rare
exomes 246/1,460,316 · genomes 13/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0212% | 4,718 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,918 |
| Finnishnot grpmax-eligible | 0.00156% | 63,930 |
| African / African-American | 0.00133% | 74,922 |
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.Arg440=
- Coding
- c.1320G>A
- MANE Select
- NM_000234
- dbSNP
- rs766768659
- Type
- single nucleotide variant
- Location
- chr19:48137019 (GRCh38)
- Structure
- AlphaFold pLDDT 75.13 · 2 PDB
- Residue 440
- the lrrct domain; a β-strand
Similar variants
- 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
- LIG1 p.Ala578Thr Uncertain significance ★★ ⚠ same type
- LIG1 p.Ala708Thr 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-arg440 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown