Is DAPK3 p.Arg412Ser (c.1234C>A) pathogenic?

DAPK3 p.Arg412Ser (c.1234C>A) is classified Uncertain significance in DAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-23). AlphaMissense: likely benign (0.3222); Absent from gnomAD v4.1.

How common is DAPK3 p.Arg412Ser (c.1234C>A) in the general population?

DAPK3 p.Arg412Ser (c.1234C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAPK3 p.Arg412Ser (c.1234C>A)?

AlphaMissense predicts likely benign (score 0.3222) — an in-silico prediction, not a clinical call.

DAPK3 p.Arg412Ser

c.1234C>A · rs769532059 · VCV2279488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3222 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,160)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3222	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -6.81	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 9	GERP 0.89, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 989 bp · p 0.0081 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,600,160). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DAPK3
Protein: p.Arg412Ser
Coding: c.1234C>A
MANE Select: NM_001348
dbSNP: rs769532059
Type: single nucleotide variant
Location: chr19:3959232 (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.Arg412Leu 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-arg412ser (accessed [today's date]).

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