Is DAPK3 p.Ala170Val (c.509C>T) pathogenic?

DAPK3 p.Ala170Val (c.509C>T) is classified Uncertain significance in DAPK3 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-01). AlphaMissense: likely benign (0.1201); Ultra-rare (popmax 0.0613%, afr).

How common is DAPK3 p.Ala170Val (c.509C>T) in the general population?

DAPK3 p.Ala170Val (c.509C>T) is ultra-rare (popmax 0.0613%, afr) (gnomAD).

What do computational predictors say about DAPK3 p.Ala170Val (c.509C>T)?

AlphaMissense predicts likely benign (score 0.1201) — an in-silico prediction, not a clinical call.

DAPK3 p.Ala170Val

c.509C>T · rs149596948 · VCV2355540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1201 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0613%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1201	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.43	donor gain · deltas
Pangolin	Δ0.33	gain · loss 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 9,641 bp · p 0.00019 · regional, not allelic
Overall
CADD	23.6	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 0.0613% African / African-American · 46/75,008 alleles

Filtering AF 0.0472% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0423%

Overall 0.00347% 56/1,613,368 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0613%	1,631
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0064%	15,619
South Asian	0.0011%	91,068
European (non-Finnish)	0.000339%	294,843

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.Ala170Val
Coding: c.509C>T
MANE Select: NM_001348
dbSNP: rs149596948
Type: single nucleotide variant
Location: chr19:3964288 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.22 · 7 PDB
Residue 170: the protein kinase domain; the 'activation segment' region

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

Similar variants

DAPK3 p.Ala198= Benign ★★ same type
DAPK3 p.Ala267Val 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-ala170val (accessed [today's date]).

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