Is CEBPD p.Phe24Leu (c.72C>A) pathogenic?

CEBPD p.Phe24Leu (c.72C>A) is classified Uncertain significance in CEBPD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-20). AlphaMissense: likely pathogenic (0.887); Very rare (popmax 0.00246%, sas).

How common is CEBPD p.Phe24Leu (c.72C>A) in the general population?

CEBPD p.Phe24Leu (c.72C>A) is very rare (popmax 0.00246%, sas) (gnomAD).

What do computational predictors say about CEBPD p.Phe24Leu (c.72C>A)?

AlphaMissense predicts likely pathogenic (score 0.887) — an in-silico prediction, not a clinical call.

CEBPD p.Phe24Leu

c.72C>A · VCV4000040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.887	likely pathogenic
REVEL	0.093	moderately benign-leaning
SaProt	LLR -4.59	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 806 bp · p 0.97 · regional, not allelic
Overall
CADD	21.8	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 0.00246% South Asian · 1/40,602 alleles

Filtering AF 0.000214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00014%

Overall 0.00055% 7/1,271,986 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00246%	40,602
European (non-Finnish)	0.000594%	168,315

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: CEBPD
Protein: p.Phe24Leu
Coding: c.72C>A
MANE Select: NM_005195
Type: single nucleotide variant
Location: chr8:47738049 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 67.03
Residue 24: the 'disordered' region

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-phe24leu (accessed [today's date]).

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