DNA2 p.Phe981=
c.2943T>C · rs538200699 · VCV710444
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.463%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.017 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.28 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP -2.6, phastCons 1 |
| Overall | ||
| CADD | 7.942 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.463%
South Asian · 410/88,592 alleles
Filtering AF
0.426%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.411%
Overall
0.0277%
444/1,603,780 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.463% | 216 |
| Remaining individualsnot grpmax-eligible | 0.0402% | 2,485 |
| Middle Eastern | 0.0332% | 3,013 |
| Admixed American | 0.0035% | 28,586 |
| European (non-Finnish) | 0.000425% | 235,381 |
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.Phe981=
- Coding
- c.2943T>C
- MANE Select
- NM_001080449
- dbSNP
- rs538200699
- Type
- single nucleotide variant
- Location
- chr10:68419058 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.82 · 1 PDB
- Residue 981
- the upf1-type sf1b helicase c-terminal domain; the 'helicase activity' region
Similar variants
- DNA2 p.Phe981fs 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-phe981 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown