Is CUL4B p.Ser5Ala (c.13T>G) pathogenic?

CUL4B p.Ser5Ala (c.13T>G) is classified Uncertain significance in CUL4B (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-10). AlphaMissense: likely benign (0.0669); Ultra-rare (popmax 0.0264%, sas).

How common is CUL4B p.Ser5Ala (c.13T>G) in the general population?

CUL4B p.Ser5Ala (c.13T>G) is ultra-rare (popmax 0.0264%, sas) (gnomAD).

What do computational predictors say about CUL4B p.Ser5Ala (c.13T>G)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

CUL4B p.Ser5Ala

c.13T>G · rs764061992 · VCV585735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -7.26	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 0.31	GERP 1.1, phastCons 0.001
Overall
CADD	6.781	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 0.0264% South Asian · 15/56,718 alleles

Filtering AF 0.0162% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.0015% 18/1,203,706 alleles · ultra-rare exomes 17/1,091,398 · genomes 1/112,308 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0264%	3,781
Remaining individualsnot grpmax-eligible	0.00633%	15,794

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: CUL4B
Protein: p.Ser5Ala
Coding: c.13T>G
MANE Select: NM_001079872 · reported on NM_003588
dbSNP: rs764061992
Type: single nucleotide variant
Location: chrX:120574605 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB
Residue 5: the 'disordered' region

Full CUL4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUL4B p.Gly5= Likely benign ★ same residue
CUL4B p.Ser5= Likely benign same residue
CUL4B p.Arg351Ter Likely pathogenic ★★ same type
CUL4B p.Arg370Ter Pathogenic ★★ same type
CUL4B p.Gln241Ter Pathogenic ★★ same type
CUL4B p.Thr813= Pathogenic/Likely pathogenic ★★ same type
CUL4B c.2592+3A>T Uncertain significance ★★ same type
CUL4B c.777-3C>T Uncertain significance ★★ same type

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/cul4b-p-ser5ala (accessed [today's date]).

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