DNA2 p.Tyr666=
c.1998C>T · rs758632207 · VCV1952970
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0112%, eas)
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 |
|---|---|---|
| Pangolin | Δ0.20 | loss · gain 0.02 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.68 | GERP -3, phastCons 0.91 |
| Overall | ||
| CADD | 8.377 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0112%
East Asian · 5/44,446 alleles
Filtering AF
0.00438%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00278%
Overall
0.0012%
19/1,588,182 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0112% | 8,889 |
| African / African-American | 0.00269% | 37,132 |
| South Asian | 0.00232% | 43,079 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,614 |
| European (non-Finnish) | 0.000771% | 129,750 |
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.Tyr666=
- Coding
- c.1998C>T
- MANE Select
- NM_001080449
- dbSNP
- rs758632207
- Type
- single nucleotide variant
- Location
- chr10:68430646 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.82 · 1 PDB
- Residue 666
- the upf1-type sf1b helicase atp-binding domain; the 'helicase activity' region
Similar variants
- DNA2 p.Tyr666Phe Uncertain significance ★★ ⚠ same residue
- 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
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-tyr666 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown