Is CUL7 p.Ser105Phe (c.314C>T) pathogenic?

CUL7 p.Ser105Phe (c.314C>T) is classified Uncertain significance in CUL7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-05-23). AlphaMissense: likely benign (0.1552); Rare (popmax 0.28%, mid); Associated with Inborn genetic diseases.

What condition is associated with CUL7 p.Ser105Phe (c.314C>T)?

CUL7 p.Ser105Phe (c.314C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CUL7 p.Ser105Phe (c.314C>T) in the general population?

CUL7 p.Ser105Phe (c.314C>T) is rare (popmax 0.28%, mid) (gnomAD).

What do computational predictors say about CUL7 p.Ser105Phe (c.314C>T)?

AlphaMissense predicts likely benign (score 0.1552) — an in-silico prediction, not a clinical call.

CUL7 p.Ser105Phe

c.314C>T · rs755714598 · VCV497923

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1552 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.28%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1552	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -7.85	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 1.7	GERP -0.41, phastCons 0.004
Regional constraint	o/e 0.90	unconstrained · MANE · 3,236 bp · p 0.0073 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.28% Middle Eastern · 17/6,062 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.00366% 59/1,614,208 alleles · rare exomes 51/1,461,848 · genomes 8/152,360 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.28%	357
South Asian	0.0373%	2,679
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	8.47e-05%	1,180,038

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.Ser105Phe
Coding: c.314C>T
MANE Select: NM_014780
dbSNP: rs755714598
Type: single nucleotide variant
Location: chr6:43052475 (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-ser105phe (accessed [today's date]).

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