DNA2 p.Ile976=
c.2928T>C · VCV3701858
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00802%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.036 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.27 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP -0.66, phastCons 1 |
| Overall | ||
| CADD | 13.34 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00802%
African / African-American · 6/74,790 alleles
Filtering AF
0.00348%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00229%
Overall
0.000372%
6/1,611,712 alleles · very rare
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.Ile976=
- Coding
- c.2928T>C
- MANE Select
- NM_001080449
- Type
- single nucleotide variant
- Location
- chr10:68419073 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.82 · 1 PDB
- Residue 976
- the upf1-type sf1b helicase c-terminal domain; the 'helicase activity' region
Similar variants
- DNA2 p.Ile976fs 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-ile976 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown