Is CIDEB p.Ala83Thr (c.247G>A) pathogenic?

CIDEB p.Ala83Thr (c.247G>A) is classified Likely benign in CIDEB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely benign (0.0764); Ultra-rare (popmax 0.09%, amr).

How common is CIDEB p.Ala83Thr (c.247G>A) in the general population?

CIDEB p.Ala83Thr (c.247G>A) is ultra-rare (popmax 0.09%, amr) (gnomAD).

What do computational predictors say about CIDEB p.Ala83Thr (c.247G>A)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

CIDEB p.Ala83Thr

c.247G>A · VCV3267349

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.09%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.16	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 -1.3	GERP -3.9
Regional constraint	o/e 1.08	unconstrained · MANE · 2,222 bp · p 0.22 · regional, not allelic
Overall
CADD	10.36	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 0.09% Admixed American · 54/60,012 alleles

Filtering AF 0.0708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0639%

Overall 0.00353% 57/1,614,148 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.09%	1,111
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000169%	590,026

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.Ala83Thr
Coding: c.247G>A
MANE Select: NM_001393339
Type: single nucleotide variant
Location: chr14:24306463 (GRCh38)
Gene constraint: LOEUF 1.542 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.40 · 1 PDB
Residue 83: the cide-n domain; a β-strand

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

Similar variants

LTB4R2 p.Thr83Ile 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-ala83thr (accessed [today's date]).

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