Is LIG4 p.Val60= (c.180C>T) pathogenic?

LIG4 p.Val60= (c.180C>T) is classified Benign/Likely benign in LIG4 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1.14%, afr); Associated with severe combined immunodeficiency due to DCLRE1C deficiency.

How common is LIG4 p.Val60= (c.180C>T) in the general population?

LIG4 p.Val60= (c.180C>T) is low-frequency (popmax 1.14%, afr) (gnomAD).

LIG4 p.Val60=

Q: What condition is associated with LIG4 p.Val60= (c.180C>T)?

LIG4 p.Val60= (c.180C>T) is associated with severe combined immunodeficiency due to DCLRE1C deficiency, DNA ligase IV deficiency (ClinVar).

Q: How is Severe combined immunodeficiency due to DCLRE1C deficiency inherited?

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

c.180C>T · rs2232637 · VCV310994

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.14%, afr)

Conditions

severe combined immunodeficiency due to DCLRE1C 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 3.7	GERP 0.042, phastCons 1
Overall
CADD	5.524	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.14% African / African-American · 850/74,744 alleles

Filtering AF 1.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.0693% 1,114/1,608,206 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.14%	88
Admixed American	0.114%	875
Middle Eastern	0.0995%	1,005
Remaining individualsnot grpmax-eligible	0.0867%	1,153
European (non-Finnish)	0.0114%	8,779
South Asian	0.00222%	45,144

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.Val60=
Coding: c.180C>T
MANE Select: NM_206937
dbSNP: rs2232637
Type: single nucleotide variant
Location: chr13:108211089 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.44 · 32 PDB

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

Disease context

severe combined immunodeficiency due to DCLRE1C deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: DNA ligase IV deficiency

For Severe combined immunodeficiency due to DCLRE1C deficiency (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-val60 (accessed [today's date]).

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