Is CEBPD p.Val224Leu (c.670G>C) pathogenic?

CEBPD p.Val224Leu (c.670G>C) is classified Uncertain significance in CEBPD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). AlphaMissense: likely benign (0.1299); Absent from gnomAD v4.1.

How common is CEBPD p.Val224Leu (c.670G>C) in the general population?

CEBPD p.Val224Leu (c.670G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEBPD p.Val224Leu (c.670G>C)?

AlphaMissense predicts likely benign (score 0.1299) — an in-silico prediction, not a clinical call.

CEBPD p.Val224Leu

c.670G>C · VCV3831249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1299 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1299	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -5.39	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 2.1	GERP -4, phastCons 0.98
Regional constraint	o/e 1.00	unconstrained · MANE · 806 bp · p 0.97 · regional, not allelic
Overall
CADD	17.6	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: CEBPD
Protein: p.Val224Leu
Coding: c.670G>C
MANE Select: NM_005195
Type: single nucleotide variant
Location: chr8:47737451 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 67.03
Residue 224: the bzip domain

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

Similar variants

CEBPD p.Ala12Gly Uncertain significance ★ ⚠ same type
CEBPD p.Ala12Thr Uncertain significance ★ ⚠ same type
CEBPD p.Ala130Val Uncertain significance ★ ⚠ same type
CEBPD p.Ala137Val Uncertain significance ★ ⚠ same type
CEBPD p.Ala173Val Uncertain significance ★ ⚠ same type
CEBPD p.Ala177Thr Uncertain significance ★ ⚠ same type
CEBPD p.Ala22Thr Uncertain significance ★ ⚠ same type
CEBPD p.Ala49Val 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/cebpd-p-val224leu (accessed [today's date]).

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