Is DNASE2 p.Thr152= (c.456C>T) pathogenic?

DNASE2 p.Thr152= (c.456C>T) is classified Likely benign in DNASE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-12). Absent from gnomAD v4.1.

How common is DNASE2 p.Thr152= (c.456C>T) in the general population?

DNASE2 p.Thr152= (c.456C>T) is absent from gnomAD v4.1 (gnomAD).

DNASE2 p.Thr152=

c.456C>T · VCV3728878

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.93	GERP -2.8, phastCons 0.081
Overall
CADD	2.854	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNASE2
Protein: p.Thr152=
Coding: c.456C>T
MANE Select: NM_001375
Type: single nucleotide variant
Location: chr19:12878725 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.52
Residue 152: a disulfide bond

Full DNASE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNASE2 c.709+4A>T Uncertain significance ★★ same type
DNASE2 p.Ala332Asp Uncertain significance ★★ ⚠ same type
DNASE2 p.Arg321Trp Uncertain significance ★★ ⚠ same type
DNASE2 p.Asn69Ser Uncertain significance ★★ ⚠ same type
DNASE2 p.Cys159Trp Uncertain significance ★★ ⚠ same type
DNASE2 p.Glu43Gly Uncertain significance ★★ ⚠ same type
DNASE2 p.Gly241Ser Uncertain significance ★★ ⚠ same type
DNASE2 p.Gly286Ser Uncertain significance ★★ ⚠ 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/dnase2-p-thr152 (accessed [today's date]).

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