Is CUL7 p.Pro613fs (c.1838del) pathogenic?

CUL7 p.Pro613fs (c.1838del) is classified Likely pathogenic in CUL7 (ClinVar, Single submitter, 1 submitter). Very rare (popmax 8.48e-05%, nfe); Associated with 3M syndrome 1.

What condition is associated with CUL7 p.Pro613fs (c.1838del)?

CUL7 p.Pro613fs (c.1838del) is associated with 3M syndrome 1 (ClinVar).

How common is CUL7 p.Pro613fs (c.1838del) in the general population?

CUL7 p.Pro613fs (c.1838del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CUL7 p.Pro613fs

c.1838del · rs2532699127 · VCV2627397

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

3M syndrome 1

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 8 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.3	GERP -2.9

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,746 alleles

Overall 0.000124% 2/1,613,740 alleles · very rare exomes 2/1,461,590 · genomes 0/152,150 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)grpmax	8.48e-05%	1,179,746

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: CUL7
Protein: p.Pro613fs
Coding: c.1838del
MANE Select: NM_014780
dbSNP: rs2532699127
Type: Deletion
Location: chr6:43048557 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.11 · 2 PDB
Residue 613: the 'disordered' region

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

Disease context

3M syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CUL7 p.Leu1046fs Pathogenic ★★ same condition
CUL7 p.Leu1308_Ser1309insTer Pathogenic/Likely pathogenic ★★ same condition
CUL7 p.Trp1127fs Pathogenic ★★ same condition
CUL7 p.Val738fs Pathogenic/Likely pathogenic ★★ same condition
CUL7 p.Val88fs Pathogenic/Likely pathogenic ★★ same condition
CUL7 c.1563_1569+5del Likely pathogenic ★ same condition
CUL7 c.4295-6_4313del Pathogenic ★ same condition
CUL7 c.727_732+18del Pathogenic ★ same condition

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-pro613fs (accessed [today's date]).

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