Is DNA2 p.Gln72Arg (c.215A>G) pathogenic?

DNA2 p.Gln72Arg (c.215A>G) is classified Uncertain significance in DNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely benign (0.0644); Very rare (popmax 0.00332%, sas).

How common is DNA2 p.Gln72Arg (c.215A>G) in the general population?

DNA2 p.Gln72Arg (c.215A>G) is very rare (popmax 0.00332%, sas) (gnomAD).

What do computational predictors say about DNA2 p.Gln72Arg (c.215A>G)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

DNA2 p.Gln72Arg

c.215A>G · rs760726047 · VCV1396154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00332%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.55	GERP -0.74, phastCons 0.001
Regional constraint	o/e 0.89	unconstrained · MANE · 57 kb · p 0.00015 · regional, not allelic
Overall
CADD	10.33	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00332% South Asian · 3/90,494 alleles

Filtering AF 0.000881% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000444%

Overall 0.000274% 4/1,459,680 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00332%	30,165
Remaining individualsnot grpmax-eligible	0.0016%	62,432

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.Gln72Arg
Coding: c.215A>G
MANE Select: NM_001080449
dbSNP: rs760726047
Type: single nucleotide variant
Location: chr10:68470023 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.82 · 1 PDB

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

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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-gln72arg (accessed [today's date]).

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