DNA2 p.Arg753His
c.2258G>A · rs751092529 · VCV2173178
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1075 | likely benign |
|---|---|---|
| REVEL | 0.351 | indeterminate |
| SaProt | LLR -6.94 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | acceptor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 57 kb · p 0.00015 · regional, not allelic |
| Overall | ||
| CADD | 21.3 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0324% | 3,086 |
| East Asian | 0.0201% | 4,986 |
| Finnishnot grpmax-eligible | 0.00626% | 15,982 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,738 |
| Admixed American | 0.00342% | 29,202 |
| African / African-American | 0.00269% | 37,164 |
| European (non-Finnish) | 0.00102% | 98,222 |
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.Arg753His
- Coding
- c.2258G>A
- MANE Select
- NM_001080449
- dbSNP
- rs751092529
- Type
- single nucleotide variant
- Location
- chr10:68422841 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.82 · 1 PDB
- Residue 753
- the upf1-type sf1b helicase atp-binding domain; the 'helicase activity' region
Similar variants
- DNA2 p.Arg753Cys Uncertain significance ★★ ⚠ same residue
- DNA2 p.Arg753Leu Uncertain significance ★ ⚠ same residue
- DNA2 c.2402+1G>A Uncertain significance ★★ same condition
- DNA2 p.Ala1003Ser Uncertain significance ★★ ⚠ same condition
- DNA2 p.Ala346Val Uncertain significance ★★ ⚠ same condition
- DNA2 p.Ala51Val Uncertain significance ★★ ⚠ same condition
- DNA2 p.Ala667Ser Uncertain significance ★★ ⚠ same condition
- DNA2 p.Ala819Val Uncertain significance ★★ ⚠ same condition
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-arg753his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown