Is DEK p.Ser271Phe (c.812C>T) pathogenic?

DEK p.Ser271Phe (c.812C>T) is classified Uncertain significance in DEK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely benign (0.1211); Ultra-rare (popmax 0.0166%, mid).

How common is DEK p.Ser271Phe (c.812C>T) in the general population?

DEK p.Ser271Phe (c.812C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about DEK p.Ser271Phe (c.812C>T)?

AlphaMissense predicts likely benign (score 0.1211) — an in-silico prediction, not a clinical call.

DEK p.Ser271Phe

c.812C>T · VCV4239281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1211 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1211	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -10.66	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 38 kb · p 0.48 · regional, not allelic
Overall
CADD	25.3	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

Grpmax group 0.0166% Middle Eastern · 1/6,034 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000343% 5/1,458,584 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,034
Remaining individualsnot grpmax-eligible	0.0016%	62,354
European (non-Finnish)	0.000254%	393,035

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.Ser271Phe
Coding: c.812C>T
MANE Select: NM_003472
Type: single nucleotide variant
Location: chr6:18237467 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.18 · 6 PDB
Residue 271: 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-ser271phe (accessed [today's date]).

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