Is LIG1 p.Arg121= (c.363T>A) pathogenic?

LIG1 p.Arg121= (c.363T>A) is classified Likely benign in LIG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). Very rare (popmax 0.00231%, eas).

How common is LIG1 p.Arg121= (c.363T>A) in the general population?

LIG1 p.Arg121= (c.363T>A) is very rare (popmax 0.00231%, eas) (gnomAD).

LIG1 p.Arg121=

c.363T>A · VCV3652834

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00231%, eas)

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 -1.8	GERP -3.1
Overall
CADD	0.694	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00231% East Asian · 1/43,300 alleles

Overall 6.26e-05% 1/1,596,688 alleles · very rare exomes 0/1,447,496 · genomes 1/149,192 · joint denominator

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: LIG1
Protein: p.Arg121=
Coding: c.363T>A
MANE Select: NM_000234
Type: single nucleotide variant
Location: chr19:48157021 (GRCh38)
Structure: AlphaFold pLDDT 75.13 · 2 PDB
Residue 121: a β-strand

Full LIG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LIG1 p.Arg121Cys Uncertain significance ★ ⚠ same residue
LIG1 p.Arg121His Uncertain significance ★ ⚠ same residue
LIG1 p.Ala269Thr Uncertain significance ★★ ⚠ same type
LIG1 p.Ala293Val Uncertain significance ★★ ⚠ same type
LIG1 p.Ala412Thr Uncertain significance ★★ ⚠ same type
LIG1 p.Ala443Thr Uncertain significance ★★ ⚠ same type
LIG1 p.Ala462Ser Uncertain significance ★★ ⚠ same type
LIG1 p.Ala545Gly Uncertain significance ★★ ⚠ same type

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/lig1-p-arg121 (accessed [today's date]).

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