Is DAPK3 p.Ala267Val (c.800C>T) pathogenic?

DAPK3 p.Ala267Val (c.800C>T) is classified Uncertain significance in DAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.107); Very rare (popmax 0.00541%, afr).

How common is DAPK3 p.Ala267Val (c.800C>T) in the general population?

DAPK3 p.Ala267Val (c.800C>T) is very rare (popmax 0.00541%, afr) (gnomAD).

What do computational predictors say about DAPK3 p.Ala267Val (c.800C>T)?

AlphaMissense predicts likely benign (score 0.107) — an in-silico prediction, not a clinical call.

DAPK3 p.Ala267Val

c.800C>T · VCV4009404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00541%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.107	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.32	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 5.2	GERP 2.1, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 989 bp · p 0.0081 · regional, not allelic
Overall
CADD	23.5	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 0.00541% African / African-American · 4/73,902 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.000383% 6/1,567,056 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00541%	18,476
South Asian	0.00111%	90,016
European (non-Finnish)	8.79e-05%	1,137,650

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: DAPK3
Protein: p.Ala267Val
Coding: c.800C>T
MANE Select: NM_001348
Type: single nucleotide variant
Location: chr19:3960087 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.22 · 7 PDB
Residue 267: the protein kinase domain; an α-helix

Full DAPK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAPK3 p.Ala198= Benign ★★ same type
DAPK3 p.Ala170Val 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
DAPK3 p.Ala428Val Uncertain significance ★ ⚠ same type
DAPK3 p.Arg134Cys 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-ala267val (accessed [today's date]).

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