Is DNA2 p.Ser307Cys (c.920C>G) pathogenic?

DNA2 p.Ser307Cys (c.920C>G) is classified Uncertain significance in DNA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-21). AlphaMissense: likely benign (0.3207); Very rare (popmax 0.00232%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNA2 p.Ser307Cys (c.920C>G)?

DNA2 p.Ser307Cys (c.920C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DNA2 p.Ser307Cys (c.920C>G) in the general population?

DNA2 p.Ser307Cys (c.920C>G) is very rare (popmax 0.00232%, nfe) (gnomAD).

What do computational predictors say about DNA2 p.Ser307Cys (c.920C>G)?

AlphaMissense predicts likely benign (score 0.3207) — an in-silico prediction, not a clinical call.

DNA2 p.Ser307Cys

c.920C>G · rs947726243 · VCV2730277

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3207 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00232%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3207	likely benign
REVEL	0.875	moderately pathogenic-leaning
SaProt	LLR -9.35	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 57 kb · p 0.00015 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00232% European (non-Finnish) · 27/1,164,782 alleles

Filtering AF 0.00159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.0017% 27/1,587,804 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.Ser307Cys
Coding: c.920C>G
MANE Select: NM_001080449
dbSNP: rs947726243
Type: single nucleotide variant
Location: chr10:68450047 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.82 · 1 PDB
Residue 307: 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.Ser307Thr 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
DNA2 p.Ala874Thr 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-ser307cys (accessed [today's date]).

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