DNA2 p.Ser88=
c.264T>C · rs749078276 · VCV385154
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.12%, mid)
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 |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.79 | GERP 1.6, phastCons 0.011 |
| Overall | ||
| CADD | 8.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.12%
Middle Eastern · 7/5,832 alleles
Filtering AF
0.0563%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0399%
Overall
0.00681%
107/1,572,098 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.12% | 833 |
| Ashkenazi Jewishnot grpmax-eligible | 0.105% | 949 |
| Remaining individualsnot grpmax-eligible | 0.0231% | 4,337 |
| Finnishnot grpmax-eligible | 0.0207% | 4,840 |
| Admixed American | 0.013% | 7,696 |
| South Asian | 0.00986% | 10,145 |
| European (non-Finnish) | 0.00233% | 42,990 |
| African / African-American | 0.00135% | 73,906 |
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.Ser88=
- Coding
- c.264T>C
- MANE Select
- NM_001080449
- dbSNP
- rs749078276
- Type
- single nucleotide variant
- Location
- chr10:68468300 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.82 · 1 PDB
- Residue 88
- the 'nuclease activity' region
Similar variants
- DNA2 p.Ser88Phe Uncertain significance ★ ⚠ same residue
- DNA2 p.Ser88Pro 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-ser88 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown