CUX1 p.Pro368=

Q: Is CUX1 p.Pro368= (c.1104G>A) pathogenic?

CUX1 p.Pro368= (c.1104G>A) is classified Benign in CUX1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-30). Common (popmax 45.8%, mid) — too common for a highly-penetrant pathogenic allele; Associated with global developmental delay with or without impaired intellectual development.

Q: What condition is associated with CUX1 p.Pro368= (c.1104G>A)?

CUX1 p.Pro368= (c.1104G>A) is associated with global developmental delay with or without impaired intellectual development (ClinVar).

Q: How common is CUX1 p.Pro368= (c.1104G>A) in the general population?

CUX1 p.Pro368= (c.1104G>A) is common (popmax 45.8%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1104G>A · rs2230104 · VCV1255430

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 45.8%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

global developmental delay with or without impaired intellectual development

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 -4.3	GERP -3.5
Overall
CADD	7.806	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 45.8% Middle Eastern · 2,775/6,056 alleles

Filtering AF 44.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 43.8%

Overall 37.1% 598,134/1,612,800 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	45.8%	2
European (non-Finnish)	38.7%	3
Ashkenazi Jewishnot grpmax-eligible	38.2%	3
South Asian	37.1%	3
African / African-American	36.9%	3
Remaining individualsnot grpmax-eligible	36.1%	3
Finnishnot grpmax-eligible	34.4%	3
Amishnot grpmax-eligible	32.1%	3
Admixed American	30.1%	3
East Asian	7.16%	14

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.Pro368=
Coding: c.1104G>A
MANE Select: NM_181552
dbSNP: rs2230104
Type: single nucleotide variant
Location: chr7:102193869 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.84 · 3 PDB

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

Disease context

global developmental delay with or without impaired intellectual development — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CUX1 c.1451-2A>G Likely pathogenic ★★ same condition
CUX1 c.1681-1G>A Pathogenic/Likely pathogenic ★★ same condition
CUX1 p.Arg661Ter Pathogenic/Likely pathogenic ★★ same condition
CUX1 p.Gln862Ter Pathogenic/Likely pathogenic ★★ same condition
CUX1 p.Glu866Ter Pathogenic/Likely pathogenic ★★ same condition
CUX1 p.Trp1188Ter Pathogenic ★★ same condition
CUX1 p.Pro1376Leu Uncertain significance ★★ ⚠ same condition
CUX1 p.Pro781Thr 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-pro368 (accessed [today's date]).

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