DNA2 p.Leu357=
c.1071A>G · VCV4759987
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00227%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor gain, 13 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.15 | GERP -2.9, phastCons 0.98 |
| Overall | ||
| CADD | 3.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00227%
South Asian · 2/87,968 alleles
Filtering AF
0.000377%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000141%
Overall
0.000346%
5/1,446,278 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00227% | 43,984 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 61,930 |
| European (non-Finnish) | 0.000171% | 586,242 |
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
- DNA2
- Protein
- p.Leu357=
- Coding
- c.1071A>G
- MANE Select
- NM_001080449
- Type
- single nucleotide variant
- Location
- chr10:68445070 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.82 · 1 PDB
- Residue 357
- 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-leu357 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown