Is CUX2 p.Asp1306= (c.3918T>C) pathogenic?

CUX2 p.Asp1306= (c.3918T>C) is classified Benign in CUX2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-30). Common (popmax 82.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with developmental and epileptic encephalopathy, 67.

What condition is associated with CUX2 p.Asp1306= (c.3918T>C)?

CUX2 p.Asp1306= (c.3918T>C) is associated with developmental and epileptic encephalopathy, 67 (ClinVar).

CUX2 p.Asp1306=

Q: How common is CUX2 p.Asp1306= (c.3918T>C) in the general population?

CUX2 p.Asp1306= (c.3918T>C) is common (popmax 82.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3918T>C · rs3803167 · VCV1239993

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 82.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

developmental and epileptic encephalopathy, 67

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3
Overall
CADD	0.053	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 82.8% East Asian · 37,084/44,814 alleles

Filtering AF 82% ClinGen BA1/BS1 input FAF95, joint · FAF99 81.8%

Overall 28.3% 457,371/1,613,356 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	82.8%	1
African / African-American	56.7%	2
Admixed American	49.8%	2
South Asian	48.1%	2
Middle Eastern	31.1%	3
Remaining individualsnot grpmax-eligible	29.8%	3
Finnishnot grpmax-eligible	23.9%	4
European (non-Finnish)	22.4%	4
Amishnot grpmax-eligible	17.6%	6
Ashkenazi Jewishnot grpmax-eligible	13.8%	7

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: CUX2
Protein: p.Asp1306=
Coding: c.3918T>C
MANE Select: NM_015267
dbSNP: rs3803167
Type: single nucleotide variant
Location: chr12:111347782 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 3 PDB
Residue 1306: the 'disordered' region

Full CUX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 67 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CUX2 p.Glu590Lys Pathogenic/Likely pathogenic ★★ same condition
CUX2 p.Ala336Thr Uncertain significance ★★ ⚠ same condition
CUX2 p.Ala544Val Uncertain significance ★★ ⚠ same condition
CUX2 p.Arg312Gln Uncertain significance ★★ ⚠ same condition
CUX2 p.Arg599Ser Uncertain significance ★★ ⚠ same condition
CUX2 p.Arg903His Uncertain significance ★★ ⚠ same condition
CUX2 p.Asp844Gly Uncertain significance ★★ ⚠ same condition
CUX2 p.Ile429Met Uncertain significance ★★ ⚠ same condition

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/cux2-p-asp1306 (accessed [today's date]).

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