Is CUX1 p.Pro918Ala (c.2752C>G) pathogenic?

CUX1 p.Pro918Ala (c.2752C>G) is classified Uncertain significance in CUX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-01). AlphaMissense: likely benign (0.0574); Absent from gnomAD v4.1.

How common is CUX1 p.Pro918Ala (c.2752C>G) in the general population?

CUX1 p.Pro918Ala (c.2752C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUX1 p.Pro918Ala (c.2752C>G)?

AlphaMissense predicts likely benign (score 0.0574) — an in-silico prediction, not a clinical call.

CUX1 p.Pro918Ala

c.2752C>G · rs782557181 · VCV3026930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0574 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0574	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.23	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 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,282 bp · p 0.00035 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CUX1
Protein: p.Pro918Ala
Coding: c.2752C>G
MANE Select: NM_181552
dbSNP: rs782557181
Type: single nucleotide variant
Location: chr7:102202049 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.84 · 3 PDB
Residue 918: 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.Pro918His Uncertain significance ★ ⚠ same residue
CUX1 p.Pro918Ser 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-pro918ala (accessed [today's date]).

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