Is DNASE2 p.Ala16Asp (c.47C>A) pathogenic?

DNASE2 p.Ala16Asp (c.47C>A) is classified Uncertain significance in DNASE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.1348); Ultra-rare (popmax 0.0555%, afr).

How common is DNASE2 p.Ala16Asp (c.47C>A) in the general population?

DNASE2 p.Ala16Asp (c.47C>A) is ultra-rare (popmax 0.0555%, afr) (gnomAD).

What do computational predictors say about DNASE2 p.Ala16Asp (c.47C>A)?

AlphaMissense predicts likely benign (score 0.1348) — an in-silico prediction, not a clinical call.

DNASE2 p.Ala16Asp

c.47C>A · rs562700068 · VCV2071054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1348 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0555%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1348	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.29, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,382 bp · p 0.057 · regional, not allelic
Overall
CADD	21.3	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 0.0555% African / African-American · 41/73,854 alleles

Filtering AF 0.042% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0373%

Overall 0.0028% 44/1,570,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0555%	1,801
Remaining individualsnot grpmax-eligible	0.00493%	20,264

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: DNASE2
Protein: p.Ala16Asp
Coding: c.47C>A
MANE Select: NM_001375
dbSNP: rs562700068
Type: single nucleotide variant
Location: chr19:12881329 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.52

Full DNASE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNASE2 c.709+4A>T Uncertain significance ★★ same type
DNASE2 p.Ala332Asp Uncertain significance ★★ ⚠ same type
DNASE2 p.Arg321Trp Uncertain significance ★★ ⚠ same type
DNASE2 p.Asn69Ser Uncertain significance ★★ ⚠ same type
DNASE2 p.Cys159Trp Uncertain significance ★★ ⚠ same type
DNASE2 p.Glu43Gly Uncertain significance ★★ ⚠ same type
DNASE2 p.Gly241Ser Uncertain significance ★★ ⚠ same type
DNASE2 p.Gly286Ser 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/dnase2-p-ala16asp (accessed [today's date]).

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