Is CREB3L1 p.Pro259fs (c.774del) pathogenic?

CREB3L1 p.Pro259fs (c.774del) is classified Likely pathogenic in CREB3L1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-13). Absent from gnomAD; Associated with osteogenesis imperfecta type 16.

What condition is associated with CREB3L1 p.Pro259fs (c.774del)?

CREB3L1 p.Pro259fs (c.774del) is associated with osteogenesis imperfecta type 16 (ClinVar).

How common is CREB3L1 p.Pro259fs (c.774del) in the general population?

CREB3L1 p.Pro259fs (c.774del) is absent from gnomAD (gnomAD).

CREB3L1 p.Pro259fs

c.774del · rs1939498274 · VCV930601

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

osteogenesis imperfecta type 16

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 -3.6	GERP -3.9

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CREB3L1
Protein: p.Pro259fs
Coding: c.774del
MANE Select: NM_052854
dbSNP: rs1939498274
Type: Deletion
Location: chr11:46312343 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.66
Residue 259: the 'disordered' region

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

Disease context

osteogenesis imperfecta type 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CREB3L1 c.1523+6del Benign/Likely benign ★★ same condition
CREB3L1 c.1259-7_1267del Likely pathogenic ★ same condition
CREB3L1 p.Phe30fs Likely pathogenic ★ same condition
CREB3L1 p.Ser210fs Uncertain significance ★ same condition
CREB3L1 p.Lys312del Pathogenic/Likely pathogenic ★★ same condition
CREB3L1 p.Ala95Val Uncertain significance ★★ ⚠ same condition
CREB3L1 p.Arg223Cys Uncertain significance ★★ ⚠ same condition
CREB3L1 p.Arg462Trp Uncertain significance ★★ ⚠ same condition

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-pro259fs (accessed [today's date]).

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