Is DAPK2 p.Ser243Asn (c.728G>A) pathogenic?

DAPK2 p.Ser243Asn (c.728G>A) is classified Uncertain significance in DAPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: likely benign (0.0737); Very rare (popmax 0.00267%, afr).

How common is DAPK2 p.Ser243Asn (c.728G>A) in the general population?

DAPK2 p.Ser243Asn (c.728G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DAPK2 p.Ser243Asn (c.728G>A)?

AlphaMissense predicts likely benign (score 0.0737) — an in-silico prediction, not a clinical call.

DAPK2 p.Ser243Asn

c.728G>A · VCV3499678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -2.83	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 6	GERP 0.99, phastCons 1
Overall
CADD	18.23	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

Grpmax group 0.00267% African / African-American · 2/74,926 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,074 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,463
European (non-Finnish)	8.47e-05%	1,180,040

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: DAPK2
Protein: p.Ser243Asn
Coding: c.728G>A
MANE Select: NM_014326
Type: single nucleotide variant
Location: chr15:63926025 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.41 · 11 PDB
Residue 243: the protein kinase domain

Full DAPK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAPK2 c.632+8G>T Benign/Likely benign ★★ same type
DAPK2 p.Arg60= Likely benign ★★ same type
DAPK2 p.Arg60Gln Likely benign ★★ same type
DAPK2 p.Arg68Gln Benign/Likely benign ★★ ⚠ same type
DAPK2 p.Thr270= Benign ★★ same type
DAPK2 p.Ala126Val Uncertain significance ★ ⚠ same type
DAPK2 p.Ala175Pro Uncertain significance ★ ⚠ same type
DAPK2 p.Ala175Val 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/dapk2-p-ser243asn (accessed [today's date]).

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