Is DAPK1 p.Val96Phe (c.286G>T) pathogenic?

DAPK1 p.Val96Phe (c.286G>T) is classified Uncertain significance in DAPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-21). AlphaMissense: likely pathogenic (0.9841); Very rare (popmax 0.00267%, afr).

How common is DAPK1 p.Val96Phe (c.286G>T) in the general population?

DAPK1 p.Val96Phe (c.286G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DAPK1 p.Val96Phe (c.286G>T)?

AlphaMissense predicts likely pathogenic (score 0.9841) — an in-silico prediction, not a clinical call.

DAPK1 p.Val96Phe

c.286G>T · rs200255856 · VCV3080065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9841	likely pathogenic · top 9% in DAPK1
REVEL	0.599	indeterminate
SaProt	LLR -13.31	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 151 kb · p 1.5e-16 · regional, not allelic
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 0.00267% African / African-American · 2/74,920 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.0128% 207/1,613,444 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.551%	181
Remaining individualsnot grpmax-eligible	0.0352%	2,838
African / African-Americangrpmax	0.00267%	37,460
European (non-Finnish)	0.0017%	58,980

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DAPK1
Protein: p.Val96Phe
Coding: c.286G>T
MANE Select: NM_004938
dbSNP: rs200255856
Type: single nucleotide variant
Location: chr9:87637944 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.74 · 79 PDB
Residue 96: the protein kinase domain; a binding site

Full DAPK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAPK1 c.1131+9C>T Benign ★★ same type
DAPK1 c.1231-6C>G Benign ★★ same type
DAPK1 c.285-6T>C Benign ★★ same type
DAPK1 c.919-10T>A Benign ★★ same type
DAPK1 c.919-9A>T Likely benign ★★ same type
DAPK1 p.Asn1347= Benign ★★ same type
DAPK1 p.Gln122= Benign ★★ same type
DAPK1 p.Gly1348Val Likely benign ★★ 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/dapk1-p-val96phe (accessed [today's date]).

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