LIG1 p.Ser447=
c.1341C>T · rs369893004 · VCV1598522
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0658%, sas)
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 -3.2 | GERP -3 |
| Overall | ||
| CADD | 1.337 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0658%
South Asian · 56/85,158 alleles
Filtering AF
0.052%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.047%
Overall
0.00747%
117/1,567,060 alleles · ultra-rare
exomes 108/1,414,856 · genomes 9/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0658% | 1,521 |
| Admixed American | 0.0466% | 2,147 |
| Remaining individualsnot grpmax-eligible | 0.0115% | 8,674 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00695% | 14,393 |
| East Asian | 0.00237% | 42,226 |
| European (non-Finnish) | 0.00225% | 44,473 |
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.Ser447=
- Coding
- c.1341C>T
- MANE Select
- NM_000234
- dbSNP
- rs369893004
- Type
- single nucleotide variant
- Location
- chr19:48136116 (GRCh38)
- Structure
- AlphaFold pLDDT 75.13 · 2 PDB
- Residue 447
- the lrrct domain; a turn
Similar variants
- LIG1 p.Ser447Asn Uncertain significance ★ ⚠ 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
- LIG1 p.Ala578Thr 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-ser447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown