Is CBLIF p.Ser82= (c.246C>T) pathogenic?

CBLIF p.Ser82= (c.246C>T) is classified Benign in CBLIF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). Common (popmax 10.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hereditary intrinsic factor deficiency.

What condition is associated with CBLIF p.Ser82= (c.246C>T)?

CBLIF p.Ser82= (c.246C>T) 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.

CBLIF p.Ser82=

Q: How common is CBLIF p.Ser82= (c.246C>T) in the general population?

CBLIF p.Ser82= (c.246C>T) is common (popmax 10.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.246C>T · rs35792306 · VCV305042

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 10.5%, eas) — too common for a highly-penetrant pathogenic allele

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 -0.34	GERP -2.6
Overall
CADD	6.242	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.5% East Asian · 4,729/44,870 alleles

Filtering AF 10.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.2%

Overall 8.03% 129,330/1,611,282 alleles · common exomes 120,185/1,459,054 · genomes 9,145/152,228 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	10.5%	9
Amishnot grpmax-eligible	9.32%	11
South Asian	9.1%	11
European (non-Finnish)	8.66%	12
Finnishnot grpmax-eligible	8.12%	12
Remaining individualsnot grpmax-eligible	7.24%	14
Ashkenazi Jewishnot grpmax-eligible	4.79%	21
Middle Eastern	4.3%	23
Admixed American	2.98%	34
African / African-American	1.39%	72

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.Ser82=
Coding: c.246C>T
MANE Select: NM_005142
dbSNP: rs35792306
Type: single nucleotide variant
Location: chr11:59843889 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69 · 2 PDB

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-ser82 (accessed [today's date]).

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