Is DNA2 p.Asp243Val (c.728A>T) pathogenic?

DNA2 p.Asp243Val (c.728A>T) is classified Uncertain significance in DNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely benign (0.1103); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DNA2 p.Asp243Val (c.728A>T)?

DNA2 p.Asp243Val (c.728A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNA2 p.Asp243Val (c.728A>T) in the general population?

DNA2 p.Asp243Val (c.728A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNA2 p.Asp243Val (c.728A>T)?

AlphaMissense predicts likely benign (score 0.1103) — an in-silico prediction, not a clinical call.

DNA2 p.Asp243Val

c.728A>T · rs1428930667 · VCV3083292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1103 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,561,448)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1103	likely benign
REVEL	0.524	indeterminate
SaProt	LLR -7.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 57 kb · p 0.00015 · regional, not allelic
Overall
CADD	22.6	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

No allele count reported in gnomAD v4.1 (AN 1,561,448). 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.Asp243Val
Coding: c.728A>T
MANE Select: NM_001080449
dbSNP: rs1428930667
Type: single nucleotide variant
Location: chr10:68450239 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.82 · 1 PDB
Residue 243: the 'nuclease activity' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNA2 p.Asp243Ala Uncertain significance ★ ⚠ same residue
DNA2 p.Asp243= Likely benign ★ same residue
DNA2 c.2402+1G>A Uncertain significance ★★ same condition
DNA2 p.Ala1003Ser Uncertain significance ★★ ⚠ same condition
DNA2 p.Ala346Val Uncertain significance ★★ same condition
DNA2 p.Ala51Val Uncertain significance ★★ ⚠ same condition
DNA2 p.Ala667Ser Uncertain significance ★★ ⚠ same condition
DNA2 p.Ala819Val Uncertain significance ★★ 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-asp243val (accessed [today's date]).

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