Is DAPK2 p.Arg41Trp (c.121C>T) pathogenic?

DAPK2 p.Arg41Trp (c.121C>T) is classified Uncertain significance in DAPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.1398); Very rare (popmax 0.00935%, afr).

How common is DAPK2 p.Arg41Trp (c.121C>T) in the general population?

DAPK2 p.Arg41Trp (c.121C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about DAPK2 p.Arg41Trp (c.121C>T)?

AlphaMissense predicts likely benign (score 0.1398) — an in-silico prediction, not a clinical call.

DAPK2 p.Arg41Trp

c.121C>T · rs779268346 · VCV2598830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1398 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1398	likely benign
REVEL	0.419	indeterminate
SaProt	LLR -10.52	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1, phastCons 1
Overall
CADD	29.5	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 0.00935% African / African-American · 7/74,902 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00391% 63/1,612,382 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,700
European (non-Finnish)	0.00466%	21,455
South Asian	0.0011%	91,076

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.Arg41Trp
Coding: c.121C>T
MANE Select: NM_014326
dbSNP: rs779268346
Type: single nucleotide variant
Location: chr15:63983726 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.41 · 11 PDB
Residue 41: the protein kinase domain; a β-strand

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

Similar variants

DAPK2 p.Arg41Gln Uncertain significance ★ ⚠ same residue
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

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-arg41trp (accessed [today's date]).

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