Is DAPK2 p.Lys151Gln (c.451A>C) pathogenic?

DAPK2 p.Lys151Gln (c.451A>C) is classified Uncertain significance in DAPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.9954); Ultra-rare (popmax 0.0445%, nfe).

How common is DAPK2 p.Lys151Gln (c.451A>C) in the general population?

DAPK2 p.Lys151Gln (c.451A>C) is ultra-rare (popmax 0.0445%, nfe) (gnomAD).

What do computational predictors say about DAPK2 p.Lys151Gln (c.451A>C)?

AlphaMissense predicts likely pathogenic (score 0.9954) — an in-silico prediction, not a clinical call.

DAPK2 p.Lys151Gln

c.451A>C · rs2140742723 · VCV2491429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0445%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9954	likely pathogenic · top 7% in DAPK2
REVEL	0.894	moderately pathogenic-leaning
SaProt	LLR -12.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 0.92, phastCons 1
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0445% European (non-Finnish) · 520/1,169,038 alleles

Filtering AF 0.0413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.0403% 584/1,449,412 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0445%	2,248
Remaining individualsnot grpmax-eligible	0.0371%	2,699
South Asian	0.0187%	5,341
Middle Eastern	0.0165%	6,044
East Asian	0.0156%	6,393
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,366
African / African-American	0.0107%	9,350
Admixed American	0.00333%	29,987
Finnishnot grpmax-eligible	0.00313%	31,926

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.Lys151Gln
Coding: c.451A>C
MANE Select: NM_014326
dbSNP: rs2140742723
Type: single nucleotide variant
Location: chr15:63971425 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.41 · 11 PDB
Residue 151: 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-lys151gln (accessed [today's date]).

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