Is CBLIF p.Ile410= (c.1230C>T) pathogenic?

CBLIF p.Ile410= (c.1230C>T) is classified Likely benign in CBLIF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). Ultra-rare (popmax 0.0846%, sas); Associated with hereditary intrinsic factor deficiency.

What condition is associated with CBLIF p.Ile410= (c.1230C>T)?

CBLIF p.Ile410= (c.1230C>T) is associated with hereditary intrinsic factor deficiency (ClinVar).

How common is CBLIF p.Ile410= (c.1230C>T) in the general population?

CBLIF p.Ile410= (c.1230C>T) is ultra-rare (popmax 0.0846%, sas) (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.Ile410=

c.1230C>T · rs150857406 · VCV778042

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0846%, sas)

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 4.9	GERP 1, phastCons 1
Overall
CADD	9.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0846% South Asian · 77/91,024 alleles

Filtering AF 0.0694% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.0112% 180/1,610,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0846%	1,182
European (non-Finnish)	0.00841%	11,891
Remaining individualsnot grpmax-eligible	0.00481%	20,788
African / African-American	0.00134%	74,882

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.Ile410=
Coding: c.1230C>T
MANE Select: NM_005142
dbSNP: rs150857406
Type: single nucleotide variant
Location: chr11:59829508 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69 · 2 PDB
Residue 410: a β-strand

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-ile410 (accessed [today's date]).

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