Is CUX1 p.Pro430fs (c.1289del) pathogenic?

CUX1 p.Pro430fs (c.1289del) is classified Pathogenic in CUX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). Very rare (popmax 0.00224%, eas); Associated with Inborn genetic diseases.

What condition is associated with CUX1 p.Pro430fs (c.1289del)?

CUX1 p.Pro430fs (c.1289del) is associated with Inborn genetic diseases (ClinVar).

How common is CUX1 p.Pro430fs (c.1289del) in the general population?

CUX1 p.Pro430fs (c.1289del) is very rare (popmax 0.00224%, eas) (gnomAD).

CUX1 p.Pro430fs

c.1289del · VCV3837504

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 15 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,706 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000551% 8/1,451,490 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,706
Admixed American	0.00171%	58,426
European (non-Finnish)	0.000511%	195,703

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: CUX1
Protein: p.Pro430fs
Coding: c.1289del
MANE Select: NM_181552
Type: Deletion
Location: chr7:102196694 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.84 · 3 PDB
Residue 430: the 'disordered' region

Full CUX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CUX1 c.3655+190_*301del Pathogenic ★ same condition
CUX1 p.Ala1415fs Likely pathogenic ★ same condition
CUX1 c.1968-3del Uncertain significance ★ same condition
CUX1 p.Pro430= Likely benign ★ same residue
CUX1 p.Pro430Ala Likely benign ★ same residue
CUX1 p.Ala1433Val Uncertain significance ★★ ⚠ same condition
CUX1 p.Asp1419Gly Uncertain significance ★★ ⚠ same condition
CUX1 p.Asp704Glu 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/cux1-p-pro430fs (accessed [today's date]).

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