Is CEBPA p.Arg339Trp (c.1015C>T) pathogenic?

CEBPA p.Arg339Trp (c.1015C>T) is classified Uncertain significance in CEBPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-30). AlphaMissense: likely pathogenic (0.9887); Very rare (popmax 0.00223%, eas).

How common is CEBPA p.Arg339Trp (c.1015C>T) in the general population?

CEBPA p.Arg339Trp (c.1015C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CEBPA p.Arg339Trp (c.1015C>T)?

AlphaMissense predicts likely pathogenic (score 0.9887) — an in-silico prediction, not a clinical call.

CEBPA p.Arg339Trp

c.1015C>T · rs1455027551 · VCV2582063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9887	likely pathogenic
REVEL	0.477	indeterminate
SaProt	LLR -14.50	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP -2.2, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 65 bp · p 0.16 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,844 alleles

Overall 0.000137% 2/1,457,990 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,844
European (non-Finnish)	8.48e-05%	1,179,606

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: CEBPA
Protein: p.Arg339Trp
Coding: c.1015C>T
MANE Select: NM_004364
dbSNP: rs1455027551
Type: single nucleotide variant
Location: chr19:33301400 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 339: the bzip domain; the 'interaction with foxo1' region; the 'leucine-zipper' region

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

Similar variants

CEBPA p.Arg339= Likely benign ★★ same residue
CEBPA p.Glu59Ter Pathogenic ★★ same type
CEBPA c.-1C>A Uncertain significance ★★ same type
CEBPA c.-4C>G Uncertain significance ★★ same type
CEBPA p.Ala113Ser Uncertain significance ★★ ⚠ same type
CEBPA p.Ala118Thr Uncertain significance ★★ ⚠ same type
CEBPA p.Ala118Val Uncertain significance ★★ ⚠ same type
CEBPA p.Ala124Val 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/cebpa-p-arg339trp (accessed [today's date]).

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