Is CUX2 p.Glu247Ter (c.739G>T) pathogenic?

CUX2 p.Glu247Ter (c.739G>T) is classified Uncertain significance in CUX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-21). Absent from gnomAD v4.1.

How common is CUX2 p.Glu247Ter (c.739G>T) in the general population?

CUX2 p.Glu247Ter (c.739G>T) is absent from gnomAD v4.1 (gnomAD).

CUX2 p.Glu247Ter

c.739G>T · rs2499790940 · VCV2502465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,575,998)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 9 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Overall
CADD	50.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,575,998). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CUX2
Protein: p.Glu247Ter
Coding: c.739G>T
MANE Select: NM_015267
dbSNP: rs2499790940
Type: single nucleotide variant
Location: chr12:111298575 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 3 PDB

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

Similar variants

CUX2 p.Glu590Lys Pathogenic/Likely pathogenic ★★ same type
CUX2 p.Ala302Ser Uncertain significance ★★ ⚠ same type
CUX2 p.Ala336Thr Uncertain significance ★★ ⚠ same type
CUX2 p.Ala544Val Uncertain significance ★★ ⚠ same type
CUX2 p.Arg312Gln Uncertain significance ★★ ⚠ same type
CUX2 p.Arg599Ser Uncertain significance ★★ ⚠ same type
CUX2 p.Arg701His Uncertain significance ★★ ⚠ same type
CUX2 p.Arg903His 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/cux2-p-glu247ter (accessed [today's date]).

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