Is DNASE1L3 p.Pro69= (c.207C>T) pathogenic?

DNASE1L3 p.Pro69= (c.207C>T) is classified Likely benign in DNASE1L3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-09-01). Absent from gnomAD v4.1; Associated with DNASE1L3-related disorder.

What condition is associated with DNASE1L3 p.Pro69= (c.207C>T)?

DNASE1L3 p.Pro69= (c.207C>T) is associated with DNASE1L3-related disorder (ClinVar).

How common is DNASE1L3 p.Pro69= (c.207C>T) in the general population?

DNASE1L3 p.Pro69= (c.207C>T) is absent from gnomAD v4.1 (gnomAD).

DNASE1L3 p.Pro69=

c.207C>T · rs2107382004 · VCV3046571

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DNASE1L3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -2.1, phastCons 1
Overall
CADD	6.786	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: DNASE1L3
Protein: p.Pro69=
Coding: c.207C>T
MANE Select: NM_004944
dbSNP: rs2107382004
Type: single nucleotide variant
Location: chr3:58208241 (GRCh38)
Gene constraint: LOEUF 1.122 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.08 · 1 PDB
Residue 69: an α-helix

Full DNASE1L3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNASE1L3-related disorder

Similar variants

DNASE1L3 p.Ala145Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
DNASE1L3 p.Met58Leu Uncertain significance ★ ⚠ same condition
DNASE1L3 p.Thr97fs Pathogenic/Likely pathogenic ★★ same condition
DNASE1L3 c.802-20C>G Uncertain significance ★★ same type
DNASE1L3 p.Ala18Thr Uncertain significance ★★ ⚠ same type
DNASE1L3 p.Ala201Thr Uncertain significance ★★ ⚠ same type
DNASE1L3 p.Ala268Gly Uncertain significance ★★ ⚠ same type
DNASE1L3 p.Arg22Lys 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/dnase1l3-p-pro69 (accessed [today's date]).

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