Is DAPK3 p.Arg28Gln (c.83G>A) pathogenic?

DAPK3 p.Arg28Gln (c.83G>A) is classified Uncertain significance in DAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: ambiguous (0.3419); Ultra-rare (popmax 0.0234%, amr).

How common is DAPK3 p.Arg28Gln (c.83G>A) in the general population?

DAPK3 p.Arg28Gln (c.83G>A) is ultra-rare (popmax 0.0234%, amr) (gnomAD).

What do computational predictors say about DAPK3 p.Arg28Gln (c.83G>A)?

AlphaMissense predicts ambiguous (score 0.3419) — an in-silico prediction, not a clinical call.

DAPK3 p.Arg28Gln

c.83G>A · VCV4658473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3419 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0234%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3419	ambiguous
REVEL	0.158	moderately benign-leaning
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.18, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 9,641 bp · p 0.00019 · regional, not allelic
Overall
CADD	24.5	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 0.0234% Admixed American · 14/59,954 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00181% 29/1,606,436 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0234%	4,282
Finnishnot grpmax-eligible	0.00324%	30,830
South Asian	0.0011%	90,940
European (non-Finnish)	0.00102%	97,959

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: DAPK3
Protein: p.Arg28Gln
Coding: c.83G>A
MANE Select: NM_001348
Type: single nucleotide variant
Location: chr19:3964971 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.22 · 7 PDB
Residue 28: the protein kinase domain; a β-strand

Full DAPK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAPK3 p.Arg28Trp Uncertain significance ★ ⚠ same residue
DAPK3 p.Ala198= Benign ★★ same type
DAPK3 p.Ala170Val Uncertain significance ★ ⚠ same type
DAPK3 p.Ala267Val Uncertain significance ★ ⚠ same type
DAPK3 p.Ala332Glu Uncertain significance ★ ⚠ same type
DAPK3 p.Ala355Ser Uncertain significance ★ ⚠ same type
DAPK3 p.Ala390Val Uncertain significance ★ ⚠ same type
DAPK3 p.Ala395Pro 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/dapk3-p-arg28gln (accessed [today's date]).

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