Is CBLIF p.Glu397Val (c.1190A>T) pathogenic?

CBLIF p.Glu397Val (c.1190A>T) is classified Uncertain significance in CBLIF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-08). AlphaMissense: likely benign (0.2232); Ultra-rare (popmax 0.0273%, nfe); Associated with hereditary intrinsic factor deficiency.

What condition is associated with CBLIF p.Glu397Val (c.1190A>T)?

CBLIF p.Glu397Val (c.1190A>T) is associated with hereditary intrinsic factor deficiency (ClinVar).

How common is CBLIF p.Glu397Val (c.1190A>T) in the general population?

CBLIF p.Glu397Val (c.1190A>T) is ultra-rare (popmax 0.0273%, 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.Glu397Val (c.1190A>T)?

AlphaMissense predicts likely benign (score 0.2232) — an in-silico prediction, not a clinical call.

CBLIF p.Glu397Val

c.1190A>T · rs150005713 · VCV1008760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2232 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0273%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary intrinsic factor deficiency

Computational evidence

Protein change
AlphaMissense	0.2232	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -2.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.73	donor loss, 2 bp away · masked 0 · deltas
Pangolin	Δ0.46	loss · gain 0.40 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.2	GERP 0.51, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.16 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0273% European (non-Finnish) · 254/930,366 alleles

Filtering AF 0.0245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.0192% 258/1,340,848 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0273%	3,663
African / African-American	0.0043%	23,253
Remaining individualsnot grpmax-eligible	0.00187%	53,542

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.Glu397Val
Coding: c.1190A>T
MANE Select: NM_005142
dbSNP: rs150005713
Type: single nucleotide variant
Location: chr11:59831680 (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-glu397val (accessed [today's date]).

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