Is CREB3L1 p.Arg293fs (c.878del) pathogenic?

CREB3L1 p.Arg293fs (c.878del) is classified Pathogenic in CREB3L1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). Very rare (popmax 0.00133%, afr).

How common is CREB3L1 p.Arg293fs (c.878del) in the general population?

CREB3L1 p.Arg293fs (c.878del) is very rare (popmax 0.00133%, afr) (gnomAD).

CREB3L1 p.Arg293fs

c.878del · rs2496169948 · VCV1914965

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 0.95, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,042 alleles

Overall 6.84e-05% 1/1,461,478 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: CREB3L1
Protein: p.Arg293fs
Coding: c.878del
MANE Select: NM_052854
dbSNP: rs2496169948
Type: Deletion
Location: chr11:46312449 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.66
Residue 293: the bzip domain; the 'basic motif' region

Full CREB3L1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CREB3L1 c.1523+6del Benign/Likely benign ★★ same type
CREB3L1 c.1259-7_1267del Likely pathogenic ★ same type
CREB3L1 p.Leu141fs Pathogenic ★ same type
CREB3L1 p.Leu409fs Pathogenic ★ same type
CREB3L1 p.Phe30fs Likely pathogenic ★ same type
CREB3L1 p.Pro259fs Likely pathogenic ★ same type
CREB3L1 c.1259-34_1259-16del Uncertain significance ★ same type
CREB3L1 p.Pro250fs 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/creb3l1-p-arg293fs (accessed [today's date]).

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