Is CUL3 p.Ile183Val (c.547A>G) pathogenic?

CUL3 p.Ile183Val (c.547A>G) is classified Likely benign in CUL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-23). AlphaMissense: likely benign (0.1032); Very rare (popmax 0.00237%, sas).

How common is CUL3 p.Ile183Val (c.547A>G) in the general population?

CUL3 p.Ile183Val (c.547A>G) is very rare (popmax 0.00237%, sas) (gnomAD).

What do computational predictors say about CUL3 p.Ile183Val (c.547A>G)?

AlphaMissense predicts likely benign (score 0.1032) — an in-silico prediction, not a clinical call.

CUL3 p.Ile183Val

c.547A>G · VCV3630543

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1032 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1032	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.35	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 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 76 kb · p 5e-41 · regional, not allelic
Overall
CADD	21.7	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 0.00237% South Asian · 2/84,562 alleles

Filtering AF 0.00062% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000477%

Overall 0.0012% 19/1,582,948 alleles · very rare exomes 16/1,430,992 · genomes 3/151,956 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00327%	30,549
South Asiangrpmax	0.00237%	42,281
Admixed American	0.00197%	50,762
African / African-American	0.00137%	72,772
European (non-Finnish)	0.00111%	90,045

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CUL3
Protein: p.Ile183Val
Coding: c.547A>G
MANE Select: NM_003590
Type: single nucleotide variant
Location: chr2:224513631 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 31 PDB
Residue 183: an α-helix

Full CUL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUL3 p.Ile183Met Uncertain significance ★ ⚠ same residue
CUL3 c.1377+1G>A Pathogenic/Likely pathogenic ★★ same type
CUL3 c.1377+4A>G Likely pathogenic ★★ same type
CUL3 c.883+1G>A Pathogenic/Likely pathogenic ★★ same type
CUL3 c.883+1G>T Pathogenic ★★ same type
CUL3 p.Arg128Cys Pathogenic/Likely pathogenic ★★ same type
CUL3 p.Arg148Ter Pathogenic ★★ same type
CUL3 p.Arg247Ter 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/cul3-p-ile183val (accessed [today's date]).

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