DNA2 p.Glu181Ter
c.541G>T · VCV3651186
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 21 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.31 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 37.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- DNA2
- Protein
- p.Glu181Ter
- Coding
- c.541G>T
- MANE Select
- NM_001080449
- Type
- single nucleotide variant
- Location
- chr10:68465713 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.82 · 1 PDB
- Residue 181
- the 'nuclease activity' region
Similar variants
- DNA2 c.588-2214A>G Pathogenic/Likely pathogenic ★★ same type
- DNA2 p.Ser640Leu Likely pathogenic ★★ ⚠ same type
- DNA2 c.2402+1G>A Uncertain significance ★★ same type
- DNA2 c.257+3A>G Uncertain significance ★★ same type
- DNA2 p.Ala1003Ser Uncertain significance ★★ ⚠ same type
- DNA2 p.Ala221Glu Uncertain significance ★★ ⚠ same type
- DNA2 p.Ala346Val Uncertain significance ★★ ⚠ same type
- DNA2 p.Ala51Val 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/dna2-p-glu181ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown