Is DNASE1 p.Gln60Arg (c.179A>G) pathogenic?

DNASE1 p.Gln60Arg (c.179A>G) is classified Uncertain significance in DNASE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). AlphaMissense: likely pathogenic (0.8055); Rare (popmax 0.104%, nfe).

How common is DNASE1 p.Gln60Arg (c.179A>G) in the general population?

DNASE1 p.Gln60Arg (c.179A>G) is rare (popmax 0.104%, nfe) (gnomAD).

What do computational predictors say about DNASE1 p.Gln60Arg (c.179A>G)?

AlphaMissense predicts likely pathogenic (score 0.8055) — an in-silico prediction, not a clinical call.

DNASE1 p.Gln60Arg

c.179A>G · VCV4542008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8055 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.104%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8055	likely pathogenic
REVEL	0.544	indeterminate
SaProt	LLR -12.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 2,576 bp · p 4.9e-14 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.104% European (non-Finnish) · 1,224/1,179,994 alleles

Filtering AF 0.0988% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0969%

Overall 0.0799% 1,289/1,613,962 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.104%	964
Remaining individualsnot grpmax-eligible	0.056%	1,786
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,289
African / African-American	0.012%	8,340
Admixed American	0.00833%	12,006
Finnishnot grpmax-eligible	0.0047%	21,279
South Asian	0.00439%	22,769

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.Gln60Arg
Coding: c.179A>G
MANE Select: NM_005223
Type: single nucleotide variant
Location: chr16:3655880 (GRCh38)
Gene constraint: LOEUF 1.46 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 94.68 · 1 PDB
Residue 60: a β-strand

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

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TRAP1 p.Ala628Val Uncertain significance ★★ ⚠ same type
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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-gln60arg (accessed [today's date]).

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