Is LIG4 p.Phe730fs (c.2190del) pathogenic?

LIG4 p.Phe730fs (c.2190del) is classified Pathogenic in LIG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). No gnomAD frequency available for this variant; Associated with DNA ligase IV deficiency.

What condition is associated with LIG4 p.Phe730fs (c.2190del)?

LIG4 p.Phe730fs (c.2190del) is associated with DNA ligase IV deficiency (ClinVar).

How common is LIG4 p.Phe730fs (c.2190del) in the general population?

LIG4 p.Phe730fs (c.2190del) is no gnomAD frequency available for this variant (gnomAD).

How is LIG4 syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LIG4 p.Phe730fs

c.2190del · rs2501583917 · VCV2703249

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

DNA ligase IV deficiency

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 -0.26	GERP -3.9

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LIG4
Protein: p.Phe730fs
Coding: c.2190del
MANE Select: NM_206937
dbSNP: rs2501583917
Type: Deletion
Location: chr13:108209079 (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 730: the brct 1 domain; an α-helix; a UniProt-annotated variant site (in lig4s)

Full LIG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNA ligase IV deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For LIG4 syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

LIG4 p.Phe730Cys Uncertain significance ★ ⚠ 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-phe730fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown