Is CBLIF p.Gln23fs (c.67_68del) pathogenic?

CBLIF p.Gln23fs (c.6768del) is classified Likely pathogenic in CBLIF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-27). Very rare (popmax 0.00167%, amr); Associated with hereditary intrinsic factor deficiency.

What condition is associated with CBLIF p.Gln23fs (c.67_68del)?

CBLIF p.Gln23fs (c.67_68del) is associated with hereditary intrinsic factor deficiency (ClinVar).

How common is CBLIF p.Gln23fs (c.67_68del) in the general population?

CBLIF p.Gln23fs (c.67_68del) is very rare (popmax 0.00167%, amr) (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.Gln23fs

c.67_68del · VCV3766532

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.77	GERP -3.7

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,004 alleles

Overall 6.85e-05% 1/1,459,726 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: CBLIF
Protein: p.Gln23fs
Coding: c.67_68del
MANE Select: NM_005142
Type: Deletion
Location: chr11:59845386 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69 · 2 PDB
Residue 23: a UniProt-annotated variant site (in)

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.Gln23Arg Benign ★★ same residue
CBLIF p.Met61fs Pathogenic ★★ same condition
CBLIF c.370+83_426del Likely pathogenic ★ same condition
CBLIF p.Thr18fs Pathogenic ★ same condition
CBLIF p.Pro394fs Uncertain significance ★ 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-gln23fs (accessed [today's date]).

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