Is AMN p.Pro381fs (c.1134_1147del) pathogenic?

AMN p.Pro381fs (c.11341147del) is classified Likely pathogenic in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). Associated with Imerslund-Grasbeck syndrome type 2.

What condition is associated with AMN p.Pro381fs (c.1134_1147del)?

AMN p.Pro381fs (c.1134_1147del) is associated with Imerslund-Grasbeck syndrome type 2 (ClinVar).

How is Imerslund-Gräsbeck syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AMN p.Pro381fs

c.1134_1147del · VCV3576411

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Imerslund-Grasbeck syndrome type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.7	GERP -2.2, phastCons 0.39

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: AMN
Protein: p.Pro381fs
Coding: c.1134_1147del
MANE Select: NM_030943
Type: Deletion
Location: chr14:102930292 (GRCh38)
Gene constraint: LOEUF 1.446 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.78 · 1 PDB

Full AMN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Imerslund-Grasbeck syndrome type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Imerslund-Gräsbeck syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Finland)

Similar variants

AMN p.Pro381Leu Uncertain significance ★ ⚠ same residue
AMN c.138_162+20del Likely pathogenic ★★ same condition
AMN c.208-13_211del Likely pathogenic ★★ same condition
AMN p.Gly5fs Pathogenic/Likely pathogenic ★★ same condition
AMN p.Gln12fs Pathogenic ★ same condition
AMN p.Gly170fs Likely pathogenic ★ same condition
AMN p.Phe104fs Likely pathogenic ★ same condition
AMN p.Pro42fs Likely pathogenic ★ 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/amn-p-pro381fs (accessed [today's date]).

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