Is LIG4 p.Ser160= (c.480T>A) pathogenic?

LIG4 p.Ser160= (c.480T>A) is classified Likely benign in LIG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). Very rare (popmax 0.000847%, nfe); Associated with DNA ligase IV deficiency.

What condition is associated with LIG4 p.Ser160= (c.480T>A)?

LIG4 p.Ser160= (c.480T>A) is associated with DNA ligase IV deficiency (ClinVar).

How common is LIG4 p.Ser160= (c.480T>A) in the general population?

LIG4 p.Ser160= (c.480T>A) is very rare (popmax 0.000847%, nfe) (gnomAD).

How is LIG4 syndrome inherited?

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

LIG4 p.Ser160=

c.480T>A · rs1878572612 · VCV2957708

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Conditions

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 2.2	GERP 1.4, phastCons 1
Overall
CADD	7.505	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000847% European (non-Finnish) · 10/1,179,960 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,614,030 alleles · very rare exomes 11/1,461,672 · genomes 0/152,358 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)grpmax	0.000847%	117,996

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.Ser160=
Coding: c.480T>A
MANE Select: NM_206937
dbSNP: rs1878572612
Type: single nucleotide variant
Location: chr13:108210789 (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 160: an α-helix

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.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
LIG4 p.Gln74Ter Pathogenic/Likely pathogenic ★★ same condition
LIG4 p.Gln773Ter Pathogenic/Likely pathogenic ★★ same condition
LIG4 p.His282Arg 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-ser160 (accessed [today's date]).

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