Is CIDEB p.Phe23Ser (c.68T>C) pathogenic?

CIDEB p.Phe23Ser (c.68T>C) is classified Uncertain significance in CIDEB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: ambiguous (0.3459); Very rare (popmax 0.000137%).

How common is CIDEB p.Phe23Ser (c.68T>C) in the general population?

CIDEB p.Phe23Ser (c.68T>C) is very rare (popmax 0.000137%) (gnomAD).

What do computational predictors say about CIDEB p.Phe23Ser (c.68T>C)?

AlphaMissense predicts ambiguous (score 0.3459) — an in-silico prediction, not a clinical call.

CIDEB p.Phe23Ser

c.68T>C · rs2502040230 · VCV3144984

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3459 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3459	ambiguous
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.38	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 2,222 bp · p 0.22 · regional, not allelic
Overall
CADD	24.7	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 0.000137%

Overall 0.000137% 2/1,461,732 alleles · very rare

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.Phe23Ser
Coding: c.68T>C
MANE Select: NM_001393339
dbSNP: rs2502040230
Type: single nucleotide variant
Location: chr14:24307489 (GRCh38)
Gene constraint: LOEUF 1.542 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.40 · 1 PDB

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

Similar variants

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
CIDEB p.Arg215Cys 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-phe23ser (accessed [today's date]).

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