Is CUL7 p.Ser365Arg (c.1093A>C) pathogenic?

CUL7 p.Ser365Arg (c.1093A>C) is classified Uncertain significance in CUL7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.8282); Very rare (popmax 0.00833%, amr).

How common is CUL7 p.Ser365Arg (c.1093A>C) in the general population?

CUL7 p.Ser365Arg (c.1093A>C) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CUL7 p.Ser365Arg (c.1093A>C)?

AlphaMissense predicts likely pathogenic (score 0.8282) — an in-silico prediction, not a clinical call.

CUL7 p.Ser365Arg

c.1093A>C · rs759702629 · VCV999261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8282 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8282	likely pathogenic · top 10% in CUL7
REVEL	0.501	indeterminate
SaProt	LLR -9.68	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.76 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 3,236 bp · p 0.0073 · regional, not allelic
Overall
CADD	25.2	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 0.00833% Admixed American · 5/60,004 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,614,042 alleles · very rare exomes 4/1,461,888 · genomes 1/152,154 · joint denominator

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.Ser365Arg
Coding: c.1093A>C
MANE Select: NM_014780
dbSNP: rs759702629
Type: single nucleotide variant
Location: chr6:43051108 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.11 · 2 PDB
Residue 365: the cph domain; a β-strand

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-ser365arg (accessed [today's date]).

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