Is CUL7 p.Asp113= (c.339C>T) pathogenic?

CUL7 p.Asp113= (c.339C>T) is classified Benign in CUL7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-08). Common (popmax 49.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with 3M syndrome 1.

What condition is associated with CUL7 p.Asp113= (c.339C>T)?

CUL7 p.Asp113= (c.339C>T) is associated with 3M syndrome 1 (ClinVar).

CUL7 p.Asp113=

Q: How common is CUL7 p.Asp113= (c.339C>T) in the general population?

CUL7 p.Asp113= (c.339C>T) is common (popmax 49.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.339C>T · rs4711738 · VCV260438

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 49.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

3M syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.1	GERP -3.7
Overall
CADD	0.891	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 49.1% African / African-American · 36,843/74,976 alleles

Filtering AF 48.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 48.5%

Overall 12.7% 205,231/1,613,918 alleles · common exomes 171,549/1,461,716 · genomes 33,682/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	49.1%	2
East Asian	24%	4
Admixed American	20.2%	5
South Asian	17.2%	6
Remaining individualsnot grpmax-eligible	14.9%	7
Middle Eastern	14.4%	7
Ashkenazi Jewishnot grpmax-eligible	9.69%	10
European (non-Finnish)	9.41%	11
Finnishnot grpmax-eligible	8.91%	11
Amishnot grpmax-eligible	1.75%	57

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.Asp113=
Coding: c.339C>T
MANE Select: NM_014780
dbSNP: rs4711738
Type: single nucleotide variant
Location: chr6:43052450 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.11 · 2 PDB

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 c.2397+1G>A Likely pathogenic ★★ same condition
CUL7 c.2660+1G>C Pathogenic ★★ same condition
CUL7 c.3356-2A>C Likely pathogenic ★★ same condition
CUL7 p.Arg1440Ter Pathogenic/Likely pathogenic ★★ same condition
CUL7 p.Arg1445Ter Pathogenic ★★ same condition
CUL7 p.Arg1573Ter Pathogenic ★★ same condition
CUL7 p.Arg382Ter Pathogenic ★★ same condition
CUL7 p.Arg550Ter Pathogenic/Likely 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-asp113 (accessed [today's date]).

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