Is LIG1 p.Asp593= (c.1779C>T) pathogenic?

LIG1 p.Asp593= (c.1779C>T) is classified Likely benign in LIG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). Very rare (popmax 0.004%, afr).

How common is LIG1 p.Asp593= (c.1779C>T) in the general population?

LIG1 p.Asp593= (c.1779C>T) is very rare (popmax 0.004%, afr) (gnomAD).

LIG1 p.Asp593=

c.1779C>T · VCV4759528

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 2.4	GERP -1.8, phastCons 1
Overall
CADD	8.413	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,926 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,002 alleles · very rare exomes 0/1,461,854 · genomes 3/152,148 · 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.Asp593=
Coding: c.1779C>T
MANE Select: NM_000234
Type: single nucleotide variant
Location: chr19:48131118 (GRCh38)
Structure: AlphaFold pLDDT 75.13 · 2 PDB
Residue 593: a β-strand; the ig-like c2-type 1 domain

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

Similar variants

LIG1 p.Asp593Glu 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
LIG1 p.Ala578Thr 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-asp593 (accessed [today's date]).

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