Is CBLIF p.Phe388Ser (c.1163T>C) pathogenic?

CBLIF p.Phe388Ser (c.1163T>C) is classified Conflicting classifications of pathogenicity in CBLIF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-12). AlphaMissense: likely pathogenic (0.9421); Very rare (popmax 0.00244%, nfe); Associated with hereditary intrinsic factor deficiency.

What condition is associated with CBLIF p.Phe388Ser (c.1163T>C)?

CBLIF p.Phe388Ser (c.1163T>C) is associated with hereditary intrinsic factor deficiency (ClinVar).

How common is CBLIF p.Phe388Ser (c.1163T>C) in the general population?

CBLIF p.Phe388Ser (c.1163T>C) is very rare (popmax 0.00244%, nfe) (gnomAD).

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.Phe388Ser (c.1163T>C)?

AlphaMissense predicts likely pathogenic (score 0.9421) — an in-silico prediction, not a clinical call.

CBLIF p.Phe388Ser

c.1163T>C · rs767310648 · VCV574163

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9421 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary intrinsic factor deficiency

Computational evidence

Protein change
AlphaMissense	0.9421	likely pathogenic · top 2% in CBLIF
REVEL	0.326	indeterminate
SaProt	LLR -14.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.16 · regional, not allelic
Overall
CADD	26.6	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 0.00244% European (non-Finnish) · 28/1,149,262 alleles

Filtering AF 0.00169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00145%

Overall 0.0019% 30/1,580,198 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00244%	41,045
Remaining individualsnot grpmax-eligible	0.00163%	61,356
African / African-American	0.00135%	74,240

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.Phe388Ser
Coding: c.1163T>C
MANE Select: NM_005142
dbSNP: rs767310648
Type: single nucleotide variant
Location: chr11:59831707 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69 · 2 PDB
Residue 388: a β-strand; a binding site

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-phe388ser (accessed [today's date]).

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