DNA2 p.Pro942=
c.2826G>A · rs200956547 · VCV508245
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.296%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.059 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.3 | GERP -2.9 |
| Overall | ||
| CADD | 6.134 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.296%
Middle Eastern · 18/6,072 alleles
Filtering AF
0.192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.158%
Overall
0.0104%
167/1,610,324 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.296% | 337 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0169% | 5,905 |
| East Asian | 0.0156% | 6,397 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,927 |
| European (non-Finnish) | 0.00967% | 10,339 |
| Admixed American | 0.00674% | 14,845 |
| Finnishnot grpmax-eligible | 0.0063% | 15,873 |
| South Asian | 0.00442% | 22,624 |
| African / African-American | 0.00268% | 37,356 |
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.Pro942=
- Coding
- c.2826G>A
- MANE Select
- NM_001080449
- dbSNP
- rs200956547
- Type
- single nucleotide variant
- Location
- chr10:68419175 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.82 · 1 PDB
- Residue 942
- the upf1-type sf1b helicase c-terminal domain; the 'helicase activity' region
Similar variants
- DNA2 p.Pro942Leu Uncertain significance ★★ ⚠ same residue
- DNA2 p.Pro942Ser 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
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-pro942 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown