Is CUX2 p.Leu796Phe (c.2386C>T) pathogenic?

CUX2 p.Leu796Phe (c.2386C>T) is classified Likely benign in CUX2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0821); Rare (popmax 0.132%, amr); Associated with Inborn genetic diseases.

What condition is associated with CUX2 p.Leu796Phe (c.2386C>T)?

CUX2 p.Leu796Phe (c.2386C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CUX2 p.Leu796Phe (c.2386C>T) in the general population?

CUX2 p.Leu796Phe (c.2386C>T) is rare (popmax 0.132%, amr) (gnomAD).

What do computational predictors say about CUX2 p.Leu796Phe (c.2386C>T)?

AlphaMissense predicts likely benign (score 0.0821) — an in-silico prediction, not a clinical call.

CUX2 p.Leu796Phe

c.2386C>T · rs775560554 · VCV726609

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0821 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0821	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -7.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 8,582 bp · p 0.88 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Admixed American · 79/59,966 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0997%

Overall 0.00682% 109/1,597,944 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.132%	759
Remaining individualsnot grpmax-eligible	0.00802%	12,466
African / African-American	0.004%	24,995
European (non-Finnish)	0.00187%	53,596

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: CUX2
Protein: p.Leu796Phe
Coding: c.2386C>T
MANE Select: NM_015267
dbSNP: rs775560554
Type: single nucleotide variant
Location: chr12:111320395 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 3 PDB

Full CUX2 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

CUX2 p.Ala302Ser Uncertain significance ★★ ⚠ same condition
CUX2 p.Ala336Thr Uncertain significance ★★ ⚠ same condition
CUX2 p.Arg312Gln Uncertain significance ★★ ⚠ same condition
CUX2 p.Arg701His Uncertain significance ★★ ⚠ same condition
CUX2 p.Arg954Cys Uncertain significance ★★ ⚠ same condition
CUX2 p.Asp1334Asn Uncertain significance ★★ ⚠ same condition
CUX2 p.Asp844Gly Uncertain significance ★★ ⚠ same condition
CUX2 p.Pro423Ala 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/cux2-p-leu796phe (accessed [today's date]).

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