Is DAPK2 p.Arg57Trp (c.169C>T) pathogenic?

DAPK2 p.Arg57Trp (c.169C>T) is classified Uncertain significance in DAPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely pathogenic (0.7994); Ultra-rare (popmax 0.0657%, mid).

How common is DAPK2 p.Arg57Trp (c.169C>T) in the general population?

DAPK2 p.Arg57Trp (c.169C>T) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

What do computational predictors say about DAPK2 p.Arg57Trp (c.169C>T)?

AlphaMissense predicts likely pathogenic (score 0.7994) — an in-silico prediction, not a clinical call.

DAPK2 p.Arg57Trp

c.169C>T · rs773075712 · VCV2467950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7994 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7994	likely pathogenic
REVEL	0.553	indeterminate
SaProt	LLR -15.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -0.28, phastCons 1
Overall
CADD	33.0	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 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00607% 98/1,613,734 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
South Asian	0.0132%	7,591
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00602%	16,620
Admixed American	0.005%	20,001
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00267%	37,468
East Asian	0.00223%	44,898

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.Arg57Trp
Coding: c.169C>T
MANE Select: NM_014326
dbSNP: rs773075712
Type: single nucleotide variant
Location: chr15:63983678 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.41 · 11 PDB
Residue 57: 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-arg57trp (accessed [today's date]).

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