Is CUL5 p.Gln75= (c.225A>G) pathogenic?

CUL5 p.Gln75= (c.225A>G) is classified Benign in CUL5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-06-29). Common (popmax 90%, eas) — too common for a highly-penetrant pathogenic allele.

CUL5 p.Gln75=

Q: How common is CUL5 p.Gln75= (c.225A>G) in the general population?

CUL5 p.Gln75= (c.225A>G) is common (popmax 90%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.225A>G · rs7117111 · VCV1272688

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 90%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.069	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.031, phastCons 1
Overall
CADD	11.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90% East Asian · 40,189/44,668 alleles

Filtering AF 89.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 88.9%

Overall 64.9% 1,035,970/1,597,410 alleles · common exomes 945,040/1,445,286 · genomes 90,930/152,124 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	90%	1
Admixed American	73.2%	1
South Asian	71.4%	1
Ashkenazi Jewishnot grpmax-eligible	66.6%	2
Remaining individualsnot grpmax-eligible	65.3%	2
Middle Eastern	64.9%	2
European (non-Finnish)	64.6%	2
Finnishnot grpmax-eligible	63.8%	2
Amishnot grpmax-eligible	61.8%	2
African / African-American	39.3%	3

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: CUL5
Protein: p.Gln75=
Coding: c.225A>G
MANE Select: NM_003478
dbSNP: rs7117111
Type: single nucleotide variant
Location: chr11:108046360 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 89.62 · 15 PDB
Residue 75: an α-helix

Full CUL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUL5 p.Ala171Thr Uncertain significance ★ same type
CUL5 p.Ala324Thr Uncertain significance ★ ⚠ same type
CUL5 p.Ala535Ser Uncertain significance ★ same type
CUL5 p.Arg247His Uncertain significance ★ ⚠ same type
CUL5 p.Arg253Gln Uncertain significance ★ ⚠ same type
CUL5 p.Arg350Gly Uncertain significance ★ ⚠ same type
CUL5 p.Arg700Lys Uncertain significance ★ ⚠ same type
CUL5 p.Arg98Gln Uncertain significance ★ ⚠ 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/cul5-p-gln75 (accessed [today's date]).

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