Is CUL7 p.Ser930fs (c.2787del) pathogenic?

CUL7 p.Ser930fs (c.2787del) is classified Pathogenic in CUL7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-04). Very rare (popmax 0.00833%, amr).

How common is CUL7 p.Ser930fs (c.2787del) in the general population?

CUL7 p.Ser930fs (c.2787del) is very rare (popmax 0.00833%, amr) (gnomAD).

CUL7 p.Ser930fs

c.2787del · rs886043872 · VCV288357

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.2	GERP 0.63, phastCons 1
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,012 alleles

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

Overall 0.000372% 6/1,614,126 alleles · very rare exomes 5/1,461,886 · genomes 1/152,240 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
European (non-Finnish)	8.47e-05%	1,180,045

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.Ser930fs
Coding: c.2787del
MANE Select: NM_014780
dbSNP: rs886043872
Type: Deletion
Location: chr6:43045662 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.11 · 2 PDB
Residue 930: the doc domain; a β-strand

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

Similar variants

CUL7 p.Ser930Asn Uncertain significance ★★ ⚠ same residue
CUL7 p.Leu1046fs Pathogenic ★★ same type
CUL7 p.Leu1308_Ser1309insTer Pathogenic/Likely pathogenic ★★ same type
CUL7 p.Leu1331fs Pathogenic ★★ same type
CUL7 p.Trp1127fs Pathogenic ★★ same type
CUL7 p.Val738fs Pathogenic/Likely pathogenic ★★ same type
CUL7 p.Val88fs Pathogenic/Likely pathogenic ★★ same type
CUL7 c.4295-9del Likely benign ★★ 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-ser930fs (accessed [today's date]).

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