Is DNASE1 p.Asp167= (c.501C>T) pathogenic?

DNASE1 p.Asp167= (c.501C>T) is classified Likely benign in DNASE1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-02). Rare (popmax 0.65%, afr); Associated with DNASE1-related disorder.

What condition is associated with DNASE1 p.Asp167= (c.501C>T)?

DNASE1 p.Asp167= (c.501C>T) is associated with DNASE1-related disorder (ClinVar).

How common is DNASE1 p.Asp167= (c.501C>T) in the general population?

DNASE1 p.Asp167= (c.501C>T) is rare (popmax 0.65%, afr) (gnomAD).

DNASE1 p.Asp167=

c.501C>T · rs59621760 · VCV3041007

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.65%, afr)

Conditions

DNASE1-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 -3.5	GERP -3.5
Overall
CADD	1.226	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.65% African / African-American · 488/75,040 alleles

Filtering AF 0.603% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.584%

Overall 0.0366% 590/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.65%	154
Admixed American	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.0384%	2,605
Finnishnot grpmax-eligible	0.0203%	4,917
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,361
European (non-Finnish)	0.00237%	42,143
East Asian	0.00223%	44,890

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: DNASE1
Protein: p.Asp167=
Coding: c.501C>T
MANE Select: NM_005223
dbSNP: rs59621760
Type: single nucleotide variant
Location: chr16:3657063 (GRCh38)
Gene constraint: LOEUF 1.46 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 94.68 · 1 PDB
Residue 167: an α-helix

Full DNASE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNASE1-related disorder

Similar variants

DNASE1 p.Asp167Asn Uncertain significance ★ ⚠ same residue
TRAP1 p.Glu471Lys Uncertain significance ★★ ⚠ same condition
TRAP1 p.Ala649Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
TRAP1 p.Pro686Arg Uncertain significance ★ ⚠ same condition
DNASE1 p.Asn78Thr Uncertain significance ⚠ same condition
DNASE1 p.Cys126= Likely benign same condition
DNASE1 p.Ile56= Likely benign same condition
DNASE1 p.Thr42= Likely benign 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/dnase1-p-asp167 (accessed [today's date]).

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