Is DNASE1 p.Arg207Cys (c.619C>T) pathogenic?

DNASE1 p.Arg207Cys (c.619C>T) is classified Conflicting classifications of pathogenicity in DNASE1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2023-12-26). AlphaMissense: likely benign (0.2794); Rare (popmax 0.346%, sas); Associated with systemic lupus erythematosus.

What condition is associated with DNASE1 p.Arg207Cys (c.619C>T)?

DNASE1 p.Arg207Cys (c.619C>T) is associated with systemic lupus erythematosus (ClinVar).

How common is DNASE1 p.Arg207Cys (c.619C>T) in the general population?

DNASE1 p.Arg207Cys (c.619C>T) is rare (popmax 0.346%, sas) (gnomAD).

How is Systemic lupus erythematosus inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNASE1 p.Arg207Cys (c.619C>T)?

AlphaMissense predicts likely benign (score 0.2794) — an in-silico prediction, not a clinical call.

DNASE1 p.Arg207Cys

c.619C>T · rs148373909 · VCV252650

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2794 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.346%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

systemic lupus erythematosus

Computational evidence

Protein change
AlphaMissense	0.2794	likely benign
REVEL	0.598	indeterminate
SaProt	LLR -12.44	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 2,576 bp · p 4.9e-14 · regional, not allelic
Overall
CADD	29.3	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 0.346% South Asian · 315/91,084 alleles

Filtering AF 0.314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.302%

Overall 0.133% 2,142/1,614,008 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.346%	289
Middle Eastern	0.297%	337
African / African-American	0.257%	389
Remaining individualsnot grpmax-eligible	0.147%	679
Admixed American	0.14%	714
European (non-Finnish)	0.119%	838
East Asian	0.0512%	1,952
Finnishnot grpmax-eligible	0.0125%	7,982
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Arg207Cys
Coding: c.619C>T
MANE Select: NM_005223
dbSNP: rs148373909
Type: single nucleotide variant
Location: chr16:3657256 (GRCh38)
Gene constraint: LOEUF 1.46 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 94.68 · 1 PDB
Residue 207: a disulfide bond; a UniProt-annotated variant site (in allele dnase1*6); an α-helix

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

Disease context

systemic lupus erythematosus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Systemic lupus erythematosus (Orphanet):

Inheritance: Not applicable
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-5 / 10 000 (France)

Similar variants

DNASE1 p.Arg207His Uncertain significance ★ ⚠ same residue
DNASE1 p.Gly127Arg Benign/Likely benign ★★ ⚠ same condition
DNASE1 p.Gln31Ter Likely pathogenic ★ same condition
DNASE1 p.Arg133Gln Uncertain significance ★ ⚠ same condition
DNASE1 p.Asp129Asn Uncertain significance ★ ⚠ same condition
DNASE1 p.Val277Ala Uncertain significance ★ ⚠ same condition
DNASE1 p.Gln258fs Uncertain significance ★ same condition
DNASE1 p.Asn40Ser 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/dnase1-p-arg207cys (accessed [today's date]).

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