Is CIDEB p.Leu92Met (c.274C>A) pathogenic?

CIDEB p.Leu92Met (c.274C>A) is classified Uncertain significance in CIDEB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1.

How common is CIDEB p.Leu92Met (c.274C>A) in the general population?

CIDEB p.Leu92Met (c.274C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIDEB p.Leu92Met (c.274C>A)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

CIDEB p.Leu92Met

c.274C>A · VCV4228931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.73	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 0.18	GERP -3.9, phastCons 0.93
Regional constraint	o/e 1.08	unconstrained · MANE · 2,222 bp · p 0.22 · regional, not allelic
Overall
CADD	16.78	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CIDEB
Protein: p.Leu92Met
Coding: c.274C>A
MANE Select: NM_001393339
Type: single nucleotide variant
Location: chr14:24306436 (GRCh38)
Gene constraint: LOEUF 1.542 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.40 · 1 PDB
Residue 92: the cide-n domain; an α-helix

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-leu92met (accessed [today's date]).

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