LIG3 p.Asp431=
c.1293C>T · VCV3339909
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0101%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.15 | GERP -2.4, phastCons 0.98 |
| Overall | ||
| CADD | 14.91 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0101%
European (non-Finnish) · 118/1,167,874 alleles
Filtering AF
0.0086%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00804%
Overall
0.00826%
131/1,586,908 alleles · ultra-rare
exomes 124/1,434,586 · genomes 7/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0101% | 9,897 |
| Remaining individualsnot grpmax-eligible | 0.0098% | 10,208 |
| African / African-American | 0.00541% | 18,471 |
| East Asian | 0.00224% | 44,566 |
| Admixed American | 0.00184% | 54,230 |
| South Asian | 0.00115% | 87,308 |
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
- LIG3
- Protein
- p.Asp431=
- Coding
- c.1293C>T
- MANE Select
- NM_013975
- Type
- single nucleotide variant
- Location
- chr17:34992530 (GRCh38)
- Gene constraint
- LOEUF 0.627 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.11 · 13 PDB
- Residue 431
- a UniProt-annotated variant site (in mtdps20); an α-helix
Similar variants
- LIG3 c.1209-2A>G Pathogenic/Likely pathogenic ★★ same type
- LIG3 p.Arg648Gln Uncertain significance ★★ ⚠ same type
- LIG3 p.Gln398Arg Uncertain significance ★★ ⚠ same type
- LIG3 p.Ser248Asn Uncertain significance ★★ ⚠ same type
- LIG3 c.1041+11C>T Benign ★★ same type
- LIG3 c.1912-3C>T Benign/Likely benign ★★ same type
- LIG3 c.2331+19G>A Benign ★★ same type
- LIG3 c.2796+6G>A Likely benign ★★ 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/lig3-p-asp431 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown