Is CEBPD p.Gln239His (c.717G>C) pathogenic?

CEBPD p.Gln239His (c.717G>C) is classified Uncertain significance in CEBPD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). AlphaMissense: ambiguous (0.4112); Ultra-rare (popmax 0.09%, mid).

How common is CEBPD p.Gln239His (c.717G>C) in the general population?

CEBPD p.Gln239His (c.717G>C) is ultra-rare (popmax 0.09%, mid) (gnomAD).

What do computational predictors say about CEBPD p.Gln239His (c.717G>C)?

AlphaMissense predicts ambiguous (score 0.4112) — an in-silico prediction, not a clinical call.

CEBPD p.Gln239His

c.717G>C · VCV3265692

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4112 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.09%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4112	ambiguous
REVEL	0.048	moderately benign-leaning
SaProt	LLR -9.50	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 806 bp · p 0.97 · regional, not allelic
Overall
CADD	23.4	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% Middle Eastern · 4/4,442 alleles

Filtering AF 0.0307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0185%

Overall 0.00306% 49/1,603,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.09%	1,111
Remaining individualsnot grpmax-eligible	0.00484%	20,642
European (non-Finnish)	0.00348%	28,710
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,370

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.Gln239His
Coding: c.717G>C
MANE Select: NM_005195
Type: single nucleotide variant
Location: chr8:47737404 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 67.03
Residue 239: the bzip domain; the 'leucine-zipper' 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-gln239his (accessed [today's date]).

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