Is CIDEB p.Pro37Thr (c.109C>A) pathogenic?

CIDEB p.Pro37Thr (c.109C>A) is classified Uncertain significance in CIDEB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely pathogenic (0.6049); Ultra-rare (popmax 0.0547%, afr).

How common is CIDEB p.Pro37Thr (c.109C>A) in the general population?

CIDEB p.Pro37Thr (c.109C>A) is ultra-rare (popmax 0.0547%, afr) (gnomAD).

What do computational predictors say about CIDEB p.Pro37Thr (c.109C>A)?

AlphaMissense predicts likely pathogenic (score 0.6049) — an in-silico prediction, not a clinical call.

CIDEB p.Pro37Thr

c.109C>A · rs144947876 · VCV3144981

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6049 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0547%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6049	likely pathogenic
REVEL	0.421	indeterminate
SaProt	LLR -8.78	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 2,222 bp · p 0.22 · regional, not allelic
Overall
CADD	24.2	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 0.0547% African / African-American · 41/75,018 alleles

Filtering AF 0.0413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0367%

Overall 0.00335% 54/1,614,144 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0547%	1,830
Middle Eastern	0.0165%	6,062
Admixed American	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.008%	12,501
European (non-Finnish)	0.000169%	590,005

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.Pro37Thr
Coding: c.109C>A
MANE Select: NM_001393339
dbSNP: rs144947876
Type: single nucleotide variant
Location: chr14:24307448 (GRCh38)
Gene constraint: LOEUF 1.542 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.40 · 1 PDB
Residue 37: 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.Pro37Leu 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-pro37thr (accessed [today's date]).

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