Is CEBPD p.Gly14Ser (c.40G>A) pathogenic?

CEBPD p.Gly14Ser (c.40G>A) is classified Uncertain significance in CEBPD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.1023); Very rare (popmax 0.0041%, sas).

How common is CEBPD p.Gly14Ser (c.40G>A) in the general population?

CEBPD p.Gly14Ser (c.40G>A) is very rare (popmax 0.0041%, sas) (gnomAD).

What do computational predictors say about CEBPD p.Gly14Ser (c.40G>A)?

AlphaMissense predicts likely benign (score 0.1023) — an in-silico prediction, not a clinical call.

CEBPD p.Gly14Ser

c.40G>A · VCV4225082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1023 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0041%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1023	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.33	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 -2.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 806 bp · p 0.97 · regional, not allelic
Overall
CADD	16.23	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 0.0041% South Asian · 1/24,362 alleles

Overall 0.000667% 1/149,862 alleles · very rare

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.Gly14Ser
Coding: c.40G>A
MANE Select: NM_005195
Type: single nucleotide variant
Location: chr8:47738081 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 67.03
Residue 14: 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-gly14ser (accessed [today's date]).

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