Is CBLIF p.Ile96= (c.288C>A) pathogenic?

CBLIF p.Ile96= (c.288C>A) is classified Likely benign in CBLIF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-25). Ultra-rare (popmax 0.06%, afr); Associated with hereditary intrinsic factor deficiency.

What condition is associated with CBLIF p.Ile96= (c.288C>A)?

CBLIF p.Ile96= (c.288C>A) is associated with hereditary intrinsic factor deficiency (ClinVar).

How common is CBLIF p.Ile96= (c.288C>A) in the general population?

CBLIF p.Ile96= (c.288C>A) is ultra-rare (popmax 0.06%, afr) (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.Ile96=

c.288C>A · rs375309032 · VCV2043431

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, afr)

Conditions

hereditary intrinsic factor deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP -4.7, phastCons 0.009
Overall
CADD	2.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.06% African / African-American · 45/75,036 alleles

Filtering AF 0.046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0411%

Overall 0.00285% 46/1,613,488 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.06%	1,667
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Ile96=
Coding: c.288C>A
MANE Select: NM_005142
dbSNP: rs375309032
Type: single nucleotide variant
Location: chr11:59843110 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69 · 2 PDB
Residue 96: a disulfide bond; an α-helix

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 c.79+1G>A Pathogenic ★★ same condition
CBLIF p.Ser46Leu Likely pathogenic ★★ ⚠ same condition
CBLIF p.Ala377Thr Uncertain significance ★★ ⚠ same condition
CBLIF p.Ala377Val Uncertain significance ★★ ⚠ same condition
CBLIF p.Arg104Gln Uncertain significance ★★ ⚠ same condition
CBLIF p.Arg352Cys Uncertain significance ★★ ⚠ same condition
CBLIF p.Arg352His Uncertain significance ★★ ⚠ same condition
CBLIF p.Gln351Glu 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/cblif-p-ile96 (accessed [today's date]).

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