Is CUX1 p.Pro915= (c.2745G>A) pathogenic?

CUX1 p.Pro915= (c.2745G>A) is classified Likely benign in CUX1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-30). Ultra-rare (popmax 0.0164%, mid); Associated with CUX1-related disorder.

What condition is associated with CUX1 p.Pro915= (c.2745G>A)?

CUX1 p.Pro915= (c.2745G>A) is associated with CUX1-related disorder (ClinVar).

How common is CUX1 p.Pro915= (c.2745G>A) in the general population?

CUX1 p.Pro915= (c.2745G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CUX1 p.Pro915=

c.2745G>A · rs781846413 · VCV3043726

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

CUX1-related disorder

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 -7.9	GERP -3.2
Overall
CADD	0.185	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.0031% 50/1,613,926 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Finnishnot grpmax-eligible	0.00937%	10,667
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	0.00305%	32,778
Admixed American	0.00167%	59,996
African / African-American	0.00134%	74,874
South Asian	0.0011%	91,082

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.Pro915=
Coding: c.2745G>A
MANE Select: NM_181552
dbSNP: rs781846413
Type: single nucleotide variant
Location: chr7:102202042 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.84 · 3 PDB
Residue 915: the 'disordered' region; a UniProt-annotated variant site (in neddms)

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

Disease context

CUX1-related disorder

Similar variants

CUX1 p.Trp1188Ter Pathogenic ★★ same condition
CUX1 p.Arg524Cys Uncertain significance ★★ same condition
CUX1 c.2908-1G>T Likely pathogenic ★ same condition
CUX1 c.1895-4A>G Uncertain significance ★ same condition
CUX1 p.Arg996Gln Uncertain significance ★ ⚠ same condition
CUX1 p.Asn655Asp Uncertain significance ★ ⚠ same condition
CUX1 p.Asp1384His Uncertain significance ★ ⚠ same condition
CUX1 p.Asp648Asn 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-pro915 (accessed [today's date]).

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