Is CUX1 p.Ser573fs (c.1717del) pathogenic?

CUX1 p.Ser573fs (c.1717del) is classified Uncertain significance in CUX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Very rare (popmax 0.00483%, nfe).

How common is CUX1 p.Ser573fs (c.1717del) in the general population?

CUX1 p.Ser573fs (c.1717del) is very rare (popmax 0.00483%, nfe) (gnomAD).

CUX1 p.Ser573fs

c.1717del · rs782125890 · VCV1695206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -2
Overall
CADD	26.7	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

Grpmax group 0.00483% European (non-Finnish) · 57/1,179,552 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00354% 57/1,610,744 alleles · very rare

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.Ser573fs
Coding: c.1717del
MANE Select: NM_181552 · reported on NM_001913
dbSNP: rs782125890
Type: Deletion
Location: chr7:102280073 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.84 · 3 PDB
Residue 573: a DNA-binding region

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

Similar variants

CUX1 p.Ser526fs Pathogenic/Likely pathogenic ★★ same type
CUX1 c.3655+190_*301del Pathogenic ★ same type
CUX1 p.Ala1415fs Likely pathogenic ★ same type
CUX1 p.Ala957fs Likely pathogenic ★ same type
CUX1 p.Gln789fs Likely pathogenic ★ same type
CUX1 p.Glu353fs Likely pathogenic ★ same type
CUX1 p.Gly439fs Likely pathogenic ★ same type
CUX1 p.Lys1068fs Pathogenic ★ 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/cux1-p-ser573fs (accessed [today's date]).

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