LIG4 p.Phe342fs
c.1026del · rs2501610215 · VCV2859019
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 2.6, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| European (non-Finnish)grpmax | 0.000339% | 294,959 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- LIG4
- Protein
- p.Phe342fs
- Coding
- c.1026del
- MANE Select
- NM_206937
- dbSNP
- rs2501610215
- Type
- Deletion
- Location
- chr13:108210243 (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 342
- a β-strand
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.Phe342= Likely benign ★ same residue
- LIG4 p.Asn294fs Pathogenic/Likely pathogenic ★★ same condition
- LIG4 p.Gln200fs Pathogenic/Likely pathogenic ★★ same condition
- LIG4 p.Glu582fs Pathogenic/Likely pathogenic ★★ same condition
- LIG4 p.His862fs Pathogenic/Likely pathogenic ★★ same condition
- LIG4 p.Ile584fs Pathogenic ★★ same condition
- LIG4 p.Leu242fs Pathogenic/Likely pathogenic ★★ same condition
- LIG4 p.Lys424fs 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-phe342fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown