Is DAPK3 p.Arg379Pro (c.1136G>C) pathogenic?

DAPK3 p.Arg379Pro (c.1136G>C) is classified Uncertain significance in DAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: ambiguous (0.349); Ultra-rare (popmax 0.0202%, nfe).

How common is DAPK3 p.Arg379Pro (c.1136G>C) in the general population?

DAPK3 p.Arg379Pro (c.1136G>C) is ultra-rare (popmax 0.0202%, nfe) (gnomAD).

What do computational predictors say about DAPK3 p.Arg379Pro (c.1136G>C)?

AlphaMissense predicts ambiguous (score 0.349) — an in-silico prediction, not a clinical call.

DAPK3 p.Arg379Pro

c.1136G>C · rs199762113 · VCV2355324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.349 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.349	ambiguous
REVEL	0.202	benign-leaning
SaProt	LLR -11.72	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 4.5	GERP -4.5, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 989 bp · p 0.0081 · regional, not allelic
Overall
CADD	24.7	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 0.0202% European (non-Finnish) · 238/1,176,098 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.0163% 260/1,591,532 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.021%	4,768
European (non-Finnish)grpmax	0.0202%	4,942
Middle Eastern	0.0165%	6,070
Finnishnot grpmax-eligible	0.00814%	12,289
Admixed American	0.00509%	19,664
African / African-American	0.00134%	74,796

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg379Pro
Coding: c.1136G>C
MANE Select: NM_001348
dbSNP: rs199762113
Type: single nucleotide variant
Location: chr19:3959330 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.22 · 7 PDB

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

Similar variants

DAPK3 p.Arg379Trp 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-arg379pro (accessed [today's date]).

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