Is DNA2 p.Gln501Ter (c.1501C>T) pathogenic?

DNA2 p.Gln501Ter (c.1501C>T) is classified Likely pathogenic in DNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). Very rare (popmax 8.48e-05%, nfe); Associated with Autosomal recessive DNA2-related disorders.

What condition is associated with DNA2 p.Gln501Ter (c.1501C>T)?

DNA2 p.Gln501Ter (c.1501C>T) is associated with Autosomal recessive DNA2-related disorders (ClinVar).

How common is DNA2 p.Gln501Ter (c.1501C>T) in the general population?

DNA2 p.Gln501Ter (c.1501C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DNA2 p.Gln501Ter

c.1501C>T · VCV4813803

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Autosomal recessive DNA2-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 21
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.67, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,850 alleles

Overall 6.84e-05% 1/1,461,592 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.Gln501Ter
Coding: c.1501C>T
MANE Select: NM_001080449
Type: single nucleotide variant
Location: chr10:68437156 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.82 · 1 PDB
Residue 501: the 'nuclease activity' region

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

Disease context

Autosomal recessive DNA2-related disorders

Similar variants

DNA2 p.Gln501= Benign ★★ same residue
DNA2 p.Ser552Leu Uncertain significance ★★ ⚠ same condition
DNA2 p.Tyr496His Uncertain significance ★★ ⚠ same condition
DNA2 c.939+1G>A Conflicting classifications of pathogenicity ★ same condition
DNA2 c.939+2T>C Uncertain significance ★ same condition
DNA2 p.Gly648Asp Uncertain significance ★ ⚠ same condition
DNA2 p.Thr585Arg Uncertain significance ★ ⚠ same condition
DNA2 c.1221-9T>C Likely benign same condition

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-gln501ter (accessed [today's date]).

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