Is CIDEB p.Arg39Cys (c.115C>T) pathogenic?

CIDEB p.Arg39Cys (c.115C>T) is classified Uncertain significance in CIDEB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: ambiguous (0.4977); Very rare (popmax 0.00668%, afr).

How common is CIDEB p.Arg39Cys (c.115C>T) in the general population?

CIDEB p.Arg39Cys (c.115C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about CIDEB p.Arg39Cys (c.115C>T)?

AlphaMissense predicts ambiguous (score 0.4977) — an in-silico prediction, not a clinical call.

CIDEB p.Arg39Cys

c.115C>T · rs376969667 · VCV2286863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Computational evidence

Protein change
AlphaMissense	0.4977	ambiguous
REVEL	0.413	indeterminate
SaProt	LLR -12.95	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 2,222 bp · p 0.22 · regional, not allelic
Overall
CADD	28.9	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 0.00668% African / African-American · 5/74,884 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00192% 31/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,977
Admixed American	0.00667%	15,001
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.00169%	59,000

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.Arg39Cys
Coding: c.115C>T
MANE Select: NM_001393339
dbSNP: rs376969667
Type: single nucleotide variant
Location: chr14:24307442 (GRCh38)
Gene constraint: LOEUF 1.542 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.40 · 1 PDB
Residue 39: 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.Arg39His 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
CIDEB p.Arg144Gln 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-arg39cys (accessed [today's date]).

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