Is CEBPD p.Ala49Val (c.146C>T) pathogenic?

CEBPD p.Ala49Val (c.146C>T) is classified Uncertain significance in CEBPD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-09). AlphaMissense: likely benign (0.1078); Very rare (popmax 0.000542%, nfe).

How common is CEBPD p.Ala49Val (c.146C>T) in the general population?

CEBPD p.Ala49Val (c.146C>T) is very rare (popmax 0.000542%, nfe) (gnomAD).

What do computational predictors say about CEBPD p.Ala49Val (c.146C>T)?

AlphaMissense predicts likely benign (score 0.1078) — an in-silico prediction, not a clinical call.

CEBPD p.Ala49Val

c.146C>T · rs1433711208 · VCV2259577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1078 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000542%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1078	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -8.15	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 0.79	GERP -2, phastCons 0.71
Regional constraint	o/e 1.00	unconstrained · MANE · 806 bp · p 0.97 · regional, not allelic
Overall
CADD	17.29	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 0.000542% European (non-Finnish) · 6/1,107,294 alleles

Filtering AF 0.000195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000128%

Overall 0.000407% 6/1,473,860 alleles · very rare exomes 6/1,323,030 · genomes 0/150,830 · joint denominator

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.Ala49Val
Coding: c.146C>T
MANE Select: NM_005195
dbSNP: rs1433711208
Type: single nucleotide variant
Location: chr8:47737975 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 67.03

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.Ala63Ser 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-ala49val (accessed [today's date]).

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