Is CUL7 p.Pro1109Ala (c.3325C>G) pathogenic?

CUL7 p.Pro1109Ala (c.3325C>G) is classified Likely benign in CUL7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). AlphaMissense: likely benign (0.0525); Ultra-rare (popmax 0.0362%, sas).

How common is CUL7 p.Pro1109Ala (c.3325C>G) in the general population?

CUL7 p.Pro1109Ala (c.3325C>G) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

What do computational predictors say about CUL7 p.Pro1109Ala (c.3325C>G)?

AlphaMissense predicts likely benign (score 0.0525) — an in-silico prediction, not a clinical call.

CUL7 p.Pro1109Ala

c.3325C>G · VCV4892078

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0525 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0525	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -6.24	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 -0.018	GERP -3.2
Regional constraint	o/e 0.85	unconstrained · MANE · 11 kb · p 6.7e-07 · regional, not allelic
Overall
CADD	7.864	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 0.0362% South Asian · 33/91,080 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00235% 38/1,614,064 alleles · ultra-rare exomes 36/1,461,728 · genomes 2/152,336 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0362%	2,760
Middle Eastern	0.0165%	6,044
Remaining individualsnot grpmax-eligible	0.0064%	15,623

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: CUL7
Protein: p.Pro1109Ala
Coding: c.3325C>G
MANE Select: NM_014780
Type: single nucleotide variant
Location: chr6:43043478 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.11 · 2 PDB

Full CUL7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUL7 c.2397+1G>A Likely pathogenic ★★ same type
CUL7 c.2398-2A>G Likely pathogenic ★★ same type
CUL7 c.2660+1G>C Pathogenic ★★ same type
CUL7 c.3356-2A>C Likely pathogenic ★★ same type
CUL7 p.Arg1440Ter Pathogenic/Likely pathogenic ★★ same type
CUL7 p.Arg1445Ter Pathogenic ★★ same type
CUL7 p.Arg1573Ter Pathogenic ★★ same type
CUL7 p.Arg382Ter 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/cul7-p-pro1109ala (accessed [today's date]).

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