Is AMN c.1257+9dup pathogenic?

AMN c.1257+9dup is classified Benign in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). Very rare (popmax 7.23e-05%); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with AMN c.1257+9dup?

AMN c.1257+9dup is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN c.1257+9dup in the general population?

AMN c.1257+9dup is very rare (popmax 7.23e-05%) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

AMN c.1257+9dup

rs1202609664 · VCV2848525

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 7.23e-05%)

Conditions

Imerslund-Grasbeck syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.5	GERP 1.2, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.23e-05%

Overall 7.23e-05% 1/1,383,698 alleles · very rare

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: AMN
Coding: c.1257+9dup
MANE Select: NM_030943
dbSNP: rs1202609664
Type: Duplication
Location: chr14:102930497 (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 — 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.Ala372_Leu374dup Uncertain significance ★★ same condition
AMN p.Val442fs Uncertain significance ★★ same condition
AMN c.1257+20dup Benign/Likely benign ★★ same condition
AMN p.Gly448_Ala449dup Benign ★★ same condition
AMN p.Ala372fs Pathogenic ★ same condition
AMN p.Arg388fs Pathogenic ★ same condition
AMN p.Gln236fs Pathogenic ★ same condition
AMN p.Leu179fs 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-c-1257-plus-9dup (accessed [today's date]).

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