Is DAPK3 p.Ala395Pro (c.1183G>C) pathogenic?

DAPK3 p.Ala395Pro (c.1183G>C) is classified Uncertain significance in DAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely pathogenic (0.6661); Absent from gnomAD v4.1.

How common is DAPK3 p.Ala395Pro (c.1183G>C) in the general population?

DAPK3 p.Ala395Pro (c.1183G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAPK3 p.Ala395Pro (c.1183G>C)?

AlphaMissense predicts likely pathogenic (score 0.6661) — an in-silico prediction, not a clinical call.

DAPK3 p.Ala395Pro

c.1183G>C · rs2039476091 · VCV3080090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6661 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6661	likely pathogenic
REVEL	0.204	benign-leaning
SaProt	LLR -13.09	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -2.8, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 989 bp · p 0.0081 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DAPK3
Protein: p.Ala395Pro
Coding: c.1183G>C
MANE Select: NM_001348
dbSNP: rs2039476091
Type: single nucleotide variant
Location: chr19:3959283 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.22 · 7 PDB

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.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-ala395pro (accessed [today's date]).

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