Is DNASE1 p.Glu35Asp (c.105G>C) pathogenic?

DNASE1 p.Glu35Asp (c.105G>C) is classified Benign/Likely benign in DNASE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-01). AlphaMissense: likely benign (0.1567); Rare (popmax 0.924%, mid).

How common is DNASE1 p.Glu35Asp (c.105G>C) in the general population?

DNASE1 p.Glu35Asp (c.105G>C) is rare (popmax 0.924%, mid) (gnomAD).

What do computational predictors say about DNASE1 p.Glu35Asp (c.105G>C)?

AlphaMissense predicts likely benign (score 0.1567) — an in-silico prediction, not a clinical call.

DNASE1 p.Glu35Asp

c.105G>C · rs34907394 · VCV2646119

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1567 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.924%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1567	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP -1.4, phastCons 0.97
Regional constraint	o/e 1.39	unconstrained · MANE · 2,576 bp · p 4.9e-14 · regional, not allelic
Overall
CADD	10.99	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 0.924% Middle Eastern · 56/6,062 alleles

Filtering AF 0.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.661%

Overall 0.467% 7,534/1,614,164 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.924%	108
Finnishnot grpmax-eligible	0.653%	153
European (non-Finnish)	0.544%	184
Remaining individualsnot grpmax-eligible	0.4%	250
Admixed American	0.318%	314
Ashkenazi Jewishnot grpmax-eligible	0.294%	340
African / African-American	0.0706%	1,416
South Asian	0.067%	1,493

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.Glu35Asp
Coding: c.105G>C
MANE Select: NM_005223
dbSNP: rs34907394
Type: single nucleotide variant
Location: chr16:3655478 (GRCh38)
Gene constraint: LOEUF 1.46 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 94.68 · 1 PDB
Residue 35: an α-helix; a functional site (involved in actin-binding)

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

Similar variants

DNASE1 p.Asn40Ser Uncertain significance ★★ ⚠ same type
DNASE1 p.Val21Met Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala465Gly Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala474Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala608Ser Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala628Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala659Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala676Val 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-glu35asp (accessed [today's date]).

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