Is CEBPB p.Pro49Leu (c.146C>T) pathogenic?

CEBPB p.Pro49Leu (c.146C>T) is classified Uncertain significance in CEBPB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: likely benign (0.1058); Ultra-rare (popmax 0.0725%, afr).

How common is CEBPB p.Pro49Leu (c.146C>T) in the general population?

CEBPB p.Pro49Leu (c.146C>T) is ultra-rare (popmax 0.0725%, afr) (gnomAD).

What do computational predictors say about CEBPB p.Pro49Leu (c.146C>T)?

AlphaMissense predicts likely benign (score 0.1058) — an in-silico prediction, not a clinical call.

CEBPB p.Pro49Leu

c.146C>T · rs761135515 · VCV2359687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1058 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0725%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1058	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -8.44	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 2.8	GERP 1.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 818 bp · p 0.69 · regional, not allelic
Overall
CADD	19.49	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

Grpmax group 0.0725% African / African-American · 49/67,626 alleles

Filtering AF 0.0563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0505%

Overall 0.00346% 50/1,443,530 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0725%	1,380
European (non-Finnish)	9.12e-05%	1,096,168

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: CEBPB
Protein: p.Pro49Leu
Coding: c.146C>T
MANE Select: NM_005194
dbSNP: rs761135515
Type: single nucleotide variant
Location: chr20:50191179 (GRCh38)
Gene constraint: LOEUF 1.677 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 61.55 · 16 PDB
Residue 49: the 'required for myc transcriptional repression' region; the 'disordered' region

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

Similar variants

CEBPB p.Ala103Thr Uncertain significance ★ ⚠ same type
CEBPB p.Ala103Val Uncertain significance ★ ⚠ same type
CEBPB p.Ala147Pro Uncertain significance ★ ⚠ same type
CEBPB p.Ala241Val Uncertain significance ★ ⚠ same type
CEBPB p.Ala247Val Uncertain significance ★ ⚠ same type
CEBPB p.Ala250Val Uncertain significance ★ ⚠ same type
CEBPB p.Ala253Thr Uncertain significance ★ ⚠ same type
CEBPB p.Ala39Pro 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/cebpb-p-pro49leu (accessed [today's date]).

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