Is CUL7 p.Pro343Ser (c.1027C>T) pathogenic?

CUL7 p.Pro343Ser (c.1027C>T) is classified Benign/Likely benign in CUL7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-05-13). AlphaMissense: likely benign (0.0842); Low-frequency (popmax 4.22%, afr); Associated with 3M syndrome 1.

What condition is associated with CUL7 p.Pro343Ser (c.1027C>T)?

CUL7 p.Pro343Ser (c.1027C>T) is associated with 3M syndrome 1 (ClinVar).

How common is CUL7 p.Pro343Ser (c.1027C>T) in the general population?

CUL7 p.Pro343Ser (c.1027C>T) is low-frequency (popmax 4.22%, afr) (gnomAD).

What do computational predictors say about CUL7 p.Pro343Ser (c.1027C>T)?

AlphaMissense predicts likely benign (score 0.0842) — an in-silico prediction, not a clinical call.

CUL7 p.Pro343Ser

c.1027C>T · rs113845886 · VCV356852

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0842 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.22%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

3M syndrome 1

Computational evidence

Protein change
AlphaMissense	0.0842	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -6.37	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 0.52	GERP 0.7
Regional constraint	o/e 0.90	unconstrained · MANE · 3,236 bp · p 0.0073 · regional, not allelic
Overall
CADD	17.25	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 4.22% African / African-American · 3,170/75,030 alleles

Filtering AF 4.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.05%

Overall 0.229% 3,691/1,614,180 alleles · low-frequency exomes 1,774/1,461,888 · genomes 1,917/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.22%	24
Middle Eastern	0.363%	276
Admixed American	0.355%	282
Remaining individualsnot grpmax-eligible	0.342%	292
South Asian	0.0362%	2,760
European (non-Finnish)	0.0033%	30,257

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.Pro343Ser
Coding: c.1027C>T
MANE Select: NM_014780
dbSNP: rs113845886
Type: single nucleotide variant
Location: chr6:43051174 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.11 · 2 PDB
Residue 343: 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.Pro343= Likely benign ★★ same residue
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

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-pro343ser (accessed [today's date]).

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