Is DNA2 p.Cys415fs (c.1244del) pathogenic?

DNA2 p.Cys415fs (c.1244del) is classified Uncertain significance in DNA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-01). Absent from gnomAD.

How common is DNA2 p.Cys415fs (c.1244del) in the general population?

DNA2 p.Cys415fs (c.1244del) is absent from gnomAD (gnomAD).

DNA2 p.Cys415fs

c.1244del · rs2493954870 · VCV2578614

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.19	GERP -3.5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DNA2
Protein: p.Cys415fs
Coding: c.1244del
MANE Select: NM_001080449
dbSNP: rs2493954870
Type: Deletion
Location: chr10:68443088 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.82 · 1 PDB
Residue 415: the 'nuclease activity' region

Full DNA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNA2 c.73_74+10del Likely pathogenic ★★ same type
DNA2 p.Asn463fs Uncertain significance ★★ same type
DNA2 p.Leu1054fs Uncertain significance ★★ same type
DNA2 p.Ser725_Leu726insTer Uncertain significance ★★ same type
DNA2 p.Ser779fs Uncertain significance ★★ same type
DNA2 p.Val418_Pro419del Uncertain significance ★★ same type
DNA2 c.1057+19del Benign ★★ same type
DNA2 c.1058-6del Benign ★★ 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-cys415fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown