Is CUL7 p.Ser55Pro (c.163T>C) pathogenic?

CUL7 p.Ser55Pro (c.163T>C) is classified Uncertain significance in CUL7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-13). AlphaMissense: likely benign (0.076); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CUL7 p.Ser55Pro (c.163T>C)?

CUL7 p.Ser55Pro (c.163T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CUL7 p.Ser55Pro (c.163T>C) in the general population?

CUL7 p.Ser55Pro (c.163T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUL7 p.Ser55Pro (c.163T>C)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

CUL7 p.Ser55Pro

c.163T>C · rs2532749636 · VCV2495577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.043	GERP -0.67
Regional constraint	o/e 0.90	unconstrained · MANE · 3,236 bp · p 0.0073 · regional, not allelic
Overall
CADD	5.329	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CUL7
Protein: p.Ser55Pro
Coding: c.163T>C
MANE Select: NM_014780
dbSNP: rs2532749636
Type: single nucleotide variant
Location: chr6:43052626 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CUL7 c.2660+1G>C Pathogenic ★★ same condition
CUL7 p.Ala272Val Uncertain significance ★★ ⚠ same condition
CUL7 p.Ala993Val Uncertain significance ★★ ⚠ same condition
CUL7 p.Arg1085Cys Uncertain significance ★★ ⚠ same condition
CUL7 p.Arg1094Cys Uncertain significance ★★ ⚠ same condition
CUL7 p.Arg1145Cys Uncertain significance ★★ ⚠ same condition
CUL7 p.Arg1190Trp Uncertain significance ★★ ⚠ same condition
CUL7 p.Arg1316Cys Uncertain significance ★★ ⚠ 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-ser55pro (accessed [today's date]).

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