Is CBLIF p.Gln23Arg (c.68A>G) pathogenic?

CBLIF p.Gln23Arg (c.68A>G) is classified Benign in CBLIF (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0546); Common (popmax 21.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary intrinsic factor deficiency.

What condition is associated with CBLIF p.Gln23Arg (c.68A>G)?

CBLIF p.Gln23Arg (c.68A>G) is associated with hereditary intrinsic factor deficiency (ClinVar).

How is Congenital intrinsic factor deficiency inherited?

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

What do computational predictors say about CBLIF p.Gln23Arg (c.68A>G)?

AlphaMissense predicts likely benign (score 0.0546) — an in-silico prediction, not a clinical call.

CBLIF p.Gln23Arg

Q: How common is CBLIF p.Gln23Arg (c.68A>G) in the general population?

CBLIF p.Gln23Arg (c.68A>G) is common (popmax 21.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.68A>G · rs35211634 · VCV1742

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0546 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 21.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary intrinsic factor deficiency

Computational evidence

Protein change
AlphaMissense	0.0546	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -4.4
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.16 · regional, not allelic
Overall
CADD	0.002	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.2% African / African-American · 15,866/74,882 alleles

Filtering AF 20.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.8%

Overall 5.82% 93,821/1,611,514 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	21.2%	5
Finnishnot grpmax-eligible	10.6%	9
Remaining individualsnot grpmax-eligible	5.57%	18
European (non-Finnish)	5.13%	19
Amishnot grpmax-eligible	4.18%	24
South Asian	3.68%	27
Admixed American	3.06%	33
East Asian	2.99%	33
Middle Eastern	2.07%	48
Ashkenazi Jewishnot grpmax-eligible	1.81%	55

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.Gln23Arg
Coding: c.68A>G
MANE Select: NM_005142
dbSNP: rs35211634
Type: single nucleotide variant
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.Gln23fs Likely pathogenic ★ same residue
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

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-gln23arg (accessed [today's date]).

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