Is DAPK3 p.Ser326Phe (c.977C>T) pathogenic?

DAPK3 p.Ser326Phe (c.977C>T) is classified Uncertain significance in DAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.3084); Ultra-rare (popmax 0.0132%, amr).

How common is DAPK3 p.Ser326Phe (c.977C>T) in the general population?

DAPK3 p.Ser326Phe (c.977C>T) is ultra-rare (popmax 0.0132%, amr) (gnomAD).

What do computational predictors say about DAPK3 p.Ser326Phe (c.977C>T)?

AlphaMissense predicts likely benign (score 0.3084) — an in-silico prediction, not a clinical call.

DAPK3 p.Ser326Phe

c.977C>T · rs780476853 · VCV2372416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3084	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 989 bp · p 0.0081 · regional, not allelic
Overall
CADD	26.4	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 0.0132% Admixed American · 7/52,980 alleles

Filtering AF 0.00617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.00328% 51/1,554,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.101%	991
Remaining individualsnot grpmax-eligible	0.0165%	6,067
Admixed Americangrpmax	0.0132%	7,569
European (non-Finnish)	0.000432%	231,516

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: DAPK3
Protein: p.Ser326Phe
Coding: c.977C>T
MANE Select: NM_001348
dbSNP: rs780476853
Type: single nucleotide variant
Location: chr19:3959489 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.22 · 7 PDB
Residue 326: a modified residue (phosphoserine; by dapk1)

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.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

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-ser326phe (accessed [today's date]).

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