Is DEK p.Pro6Leu (c.17C>T) pathogenic?

DEK p.Pro6Leu (c.17C>T) is classified Uncertain significance in DEK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.1284); Very rare (popmax 0.00169%, amr).

How common is DEK p.Pro6Leu (c.17C>T) in the general population?

DEK p.Pro6Leu (c.17C>T) is very rare (popmax 0.00169%, amr) (gnomAD).

What do computational predictors say about DEK p.Pro6Leu (c.17C>T)?

AlphaMissense predicts likely benign (score 0.1284) — an in-silico prediction, not a clinical call.

DEK p.Pro6Leu

c.17C>T · rs775386492 · VCV2492789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1284 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1284	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -7.93	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 8.2	GERP 0.56, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 38 kb · p 0.48 · regional, not allelic
Overall
CADD	24.4	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 0.00169% Admixed American · 1/59,226 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.00112% 18/1,611,496 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00169%	59,226
Remaining individualsnot grpmax-eligible	0.0016%	62,362
African / African-American	0.00134%	74,706
European (non-Finnish)	0.00127%	78,608

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: DEK
Protein: p.Pro6Leu
Coding: c.17C>T
MANE Select: NM_003472
dbSNP: rs775386492
Type: single nucleotide variant
Location: chr6:18263971 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.18 · 6 PDB
Residue 6: the 'disordered' region

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

Similar variants

DEK p.Ala18Gly Uncertain significance ★ ⚠ same type
DEK p.Ala214Val Uncertain significance ★ ⚠ same type
DEK p.Ala334Asp Uncertain significance ★ ⚠ same type
DEK p.Ala3Val Uncertain significance ★ ⚠ same type
DEK p.Ala7Thr Uncertain significance ★ ⚠ same type
DEK p.Ala81Glu Uncertain significance ★ ⚠ same type
DEK p.Arg208Gln Uncertain significance ★ ⚠ same type
DEK p.Arg29Gly 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/dek-p-pro6leu (accessed [today's date]).

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