Is DEK p.Ser279Arg (c.837T>A) pathogenic?

DEK p.Ser279Arg (c.837T>A) is classified Uncertain significance in DEK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely pathogenic (0.5948); Ultra-rare (popmax 0.0766%, afr).

How common is DEK p.Ser279Arg (c.837T>A) in the general population?

DEK p.Ser279Arg (c.837T>A) is ultra-rare (popmax 0.0766%, afr) (gnomAD).

What do computational predictors say about DEK p.Ser279Arg (c.837T>A)?

AlphaMissense predicts likely pathogenic (score 0.5948) — an in-silico prediction, not a clinical call.

DEK p.Ser279Arg

c.837T>A · VCV3271480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5948 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0766%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5948	likely pathogenic
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.57, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 38 kb · p 0.48 · regional, not allelic
Overall
CADD	19.46	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

Grpmax group 0.0766% African / African-American · 57/74,392 alleles

Filtering AF 0.0606% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0549%

Overall 0.00416% 67/1,610,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0766%	1,305
Remaining individualsnot grpmax-eligible	0.00963%	10,389
Admixed American	0.00674%	14,842

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.Ser279Arg
Coding: c.837T>A
MANE Select: NM_003472
Type: single nucleotide variant
Location: chr6:18237442 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.18 · 6 PDB
Residue 279: a modified residue (adp-ribosylserine); 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-ser279arg (accessed [today's date]).

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