Is CIDEB p.Arg48Trp (c.142C>T) pathogenic?

CIDEB p.Arg48Trp (c.142C>T) is classified Uncertain significance in CIDEB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: ambiguous (0.3579); Ultra-rare (popmax 0.0164%, mid).

How common is CIDEB p.Arg48Trp (c.142C>T) in the general population?

CIDEB p.Arg48Trp (c.142C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CIDEB p.Arg48Trp (c.142C>T)?

AlphaMissense predicts ambiguous (score 0.3579) — an in-silico prediction, not a clinical call.

CIDEB p.Arg48Trp

c.142C>T · rs780541536 · VCV2227097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3579 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
AlphaMissense	0.3579	ambiguous
REVEL	0.397	indeterminate
SaProt	LLR -11.70	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -3.9, phastCons 0.33
Regional constraint	o/e 1.08	unconstrained · MANE · 2,222 bp · p 0.22 · regional, not allelic
Overall
CADD	21.0	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.0018% 29/1,613,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,289
Middle Easterngrpmax	0.0164%	6,080
Admixed American	0.005%	19,992
South Asian	0.00439%	22,772
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000932%	107,266

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CIDEB
Protein: p.Arg48Trp
Coding: c.142C>T
MANE Select: NM_001393339
dbSNP: rs780541536
Type: single nucleotide variant
Location: chr14:24307415 (GRCh38)
Gene constraint: LOEUF 1.542 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.40 · 1 PDB
Residue 48: the cide-n domain; a β-strand

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

Similar variants

CIDEB p.Arg48Gln Uncertain significance ★ ⚠ same residue
LTB4R2 p.Trp48Arg Uncertain significance ★ ⚠ same residue
LTB4R2 p.Pro130Ser Benign ★★ same type
LTB4R2 p.Thr188= Benign ★★ same type
CIDEB p.Ala154Asp Uncertain significance ★ ⚠ same type
CIDEB p.Ala203Pro Uncertain significance ★ ⚠ same type
CIDEB p.Ala63Glu Uncertain significance ★ ⚠ same type
CIDEB p.Arg122Pro 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/cideb-p-arg48trp (accessed [today's date]).

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