LIG4 p.Pro809=
c.2427T>A · rs1327975983 · VCV2834761
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
DNA ligase IV deficiency
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 -0.63 | GERP -3.9 |
| Overall | ||
| CADD | 2.574 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- LIG4
- Protein
- p.Pro809=
- Coding
- c.2427T>A
- MANE Select
- NM_206937
- dbSNP
- rs1327975983
- Type
- single nucleotide variant
- Location
- chr13:108208842 (GRCh38)
- Gene constraint
- LOEUF 1.043 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.44 · 32 PDB
- Residue 809
- an α-helix; the brct 2 domain; a UniProt-annotated variant site (in lig4s)
Disease context
DNA ligase IV deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor LIG4 syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- LIG4 p.Pro809Ala Uncertain significance ★★ ⚠ same residue
- LIG4 p.Pro809Leu Uncertain significance ★★ ⚠ same residue
- LIG4 p.Pro809fs Pathogenic ★ same residue
- LIG4 p.Arg278His Pathogenic ★★ same condition
- LIG4 p.Arg278Leu Pathogenic ★★ same condition
- LIG4 p.Arg293Ter Pathogenic/Likely pathogenic ★★ same condition
- LIG4 p.Arg580Ter Pathogenic/Likely pathogenic ★★ same condition
- LIG4 p.Arg814Ter Pathogenic/Likely pathogenic ★★ same condition
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/lig4-p-pro809 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown