Is DEK p.Ala3Val (c.8C>T) pathogenic?

DEK p.Ala3Val (c.8C>T) is classified Uncertain significance in DEK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). AlphaMissense: likely benign (0.1489); Very rare (popmax 0.00551%, sas).

How common is DEK p.Ala3Val (c.8C>T) in the general population?

DEK p.Ala3Val (c.8C>T) is very rare (popmax 0.00551%, sas) (gnomAD).

What do computational predictors say about DEK p.Ala3Val (c.8C>T)?

AlphaMissense predicts likely benign (score 0.1489) — an in-silico prediction, not a clinical call.

DEK p.Ala3Val

c.8C>T · rs767695288 · VCV3081364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1489	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.30	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 8.1	GERP 0.83, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 38 kb · p 0.48 · regional, not allelic
Overall
CADD	23.7	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 0.00551% South Asian · 5/90,762 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000435% 7/1,610,184 alleles · very rare exomes 7/1,457,936 · genomes 0/152,248 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00551%	18,152
Finnishnot grpmax-eligible	0.00157%	63,852
European (non-Finnish)	8.48e-05%	1,178,616

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.Ala3Val
Coding: c.8C>T
MANE Select: NM_003472
dbSNP: rs767695288
Type: single nucleotide variant
Location: chr6:18263980 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.18 · 6 PDB
Residue 3: 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.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
DEK p.Asn281Asp 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-ala3val (accessed [today's date]).

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