Is CBLIF p.Pro394fs (c.1181del) pathogenic?

CBLIF p.Pro394fs (c.1181del) is classified Uncertain significance in CBLIF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-04). Absent from gnomAD; Associated with hereditary intrinsic factor deficiency.

What condition is associated with CBLIF p.Pro394fs (c.1181del)?

CBLIF p.Pro394fs (c.1181del) is associated with hereditary intrinsic factor deficiency (ClinVar).

How common is CBLIF p.Pro394fs (c.1181del) in the general population?

CBLIF p.Pro394fs (c.1181del) is absent from gnomAD (gnomAD).

How is Congenital intrinsic factor deficiency inherited?

Typically Autosomal recessive, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

CBLIF p.Pro394fs

c.1181del · rs1565206584 · VCV581451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary intrinsic factor deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (8 of 9, 11 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 0.6, phastCons 1

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: CBLIF
Protein: p.Pro394fs
Coding: c.1181del
MANE Select: NM_005142
dbSNP: rs1565206584
Type: Deletion
Location: chr11:59831689 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69 · 2 PDB
Residue 394: a binding site

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

Disease context

hereditary intrinsic factor deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital intrinsic factor deficiency (Orphanet):

Inheritance: Autosomal recessive, Not applicable
Onset: Childhood

Similar variants

CBLIF p.Pro394Ser Uncertain significance ★★ ⚠ same residue
CBLIF p.Met61fs Pathogenic ★★ same condition
CBLIF c.370+83_426del Likely pathogenic ★ same condition
CBLIF p.Gln23fs Likely pathogenic ★ same condition
CBLIF p.Thr18fs Pathogenic ★ same condition
CBLIF p.Asn54fs Pathogenic same condition
CBLIF c.79+1G>A Pathogenic ★★ same condition
CBLIF p.Ser46Leu Likely pathogenic ★★ ⚠ 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/cblif-p-pro394fs (accessed [today's date]).

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