Is CUX1 p.Pro1417= (c.4251C>T) pathogenic?

CUX1 p.Pro1417= (c.4251C>T) is classified Likely benign in CUX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). Ultra-rare (popmax 0.0463%, nfe).

How common is CUX1 p.Pro1417= (c.4251C>T) in the general population?

CUX1 p.Pro1417= (c.4251C>T) is ultra-rare (popmax 0.0463%, nfe) (gnomAD).

CUX1 p.Pro1417=

c.4251C>T · rs868908604 · VCV1695204

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0463%, nfe)

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 1.4	GERP -1.9, phastCons 1
Overall
CADD	12.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0463% European (non-Finnish) · 402/867,556 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0411%

Overall 0.0418% 437/1,044,418 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0489%	2,045
European (non-Finnish)grpmax	0.0463%	2,158
South Asian	0.0448%	2,230
Admixed American	0.0113%	8,856
African / African-American	0.0087%	11,490
Finnishnot grpmax-eligible	0.0058%	17,246

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1417=
Coding: c.4251C>T
MANE Select: NM_181552
dbSNP: rs868908604
Type: single nucleotide variant
Location: chr7:102248775 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.84 · 3 PDB
Residue 1417: the 'disordered' region; a UniProt-annotated variant site (in neddms)

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

Similar variants

CUX1 p.Pro1417Ala Uncertain significance ★ ⚠ same residue
CUX1 p.Pro1417Leu Uncertain significance ★ ⚠ same residue
CUX1 c.1451-2A>G Likely pathogenic ★★ same type
CUX1 c.1681-1G>A Pathogenic/Likely pathogenic ★★ same type
CUX1 p.Arg661Ter Pathogenic/Likely pathogenic ★★ same type
CUX1 p.Gln862Ter Pathogenic/Likely pathogenic ★★ same type
CUX1 p.Glu866Ter Pathogenic/Likely pathogenic ★★ same type
CUX1 p.Trp1188Ter 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-pro1417 (accessed [today's date]).

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