Is CUX1 p.Pro430Ala (c.1288C>G) pathogenic?

CUX1 p.Pro430Ala (c.1288C>G) is classified Likely benign in CUX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). AlphaMissense: likely benign (0.0558); Ultra-rare (popmax 0.0111%, nfe).

How common is CUX1 p.Pro430Ala (c.1288C>G) in the general population?

CUX1 p.Pro430Ala (c.1288C>G) is ultra-rare (popmax 0.0111%, nfe) (gnomAD).

What do computational predictors say about CUX1 p.Pro430Ala (c.1288C>G)?

AlphaMissense predicts likely benign (score 0.0558) — an in-silico prediction, not a clinical call.

CUX1 p.Pro430Ala

c.1288C>G · rs200423314 · VCV2657861

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0558 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0558	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.47	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 127 kb · p 0.013 · regional, not allelic
Overall
CADD	24.5	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 0.0111% European (non-Finnish) · 130/1,176,112 alleles

Filtering AF 0.00947% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00891%

Overall 0.00883% 142/1,607,718 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0111%	9,047
East Asian	0.00893%	11,193
Finnishnot grpmax-eligible	0.00627%	15,947
Admixed American	0.00337%	29,649
Remaining individualsnot grpmax-eligible	0.00322%	31,058

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.Pro430Ala
Coding: c.1288C>G
MANE Select: NM_181552
dbSNP: rs200423314
Type: single nucleotide variant
Location: chr7:102196699 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.84 · 3 PDB
Residue 430: the 'disordered' region

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

Similar variants

CUX1 p.Pro430= Likely benign ★ same residue
CUX1 p.Pro430fs Pathogenic ★ 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-pro430ala (accessed [today's date]).

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