Is AMN c.760+12del pathogenic?

AMN c.760+12del is classified Benign in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-26). Very rare (popmax 0.000144%); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with AMN c.760+12del?

AMN c.760+12del is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN c.760+12del in the general population?

AMN c.760+12del is very rare (popmax 0.000144%) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

AMN c.760+12del

VCV4733051

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000144%)

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 +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.12	GERP -1.7

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000144%

Overall 0.000144% 2/1,387,494 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00197%	50,642
Remaining individualsnot grpmax-eligible	0.00167%	59,846

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.760+12del
MANE Select: NM_030943
Type: Deletion
Location: chr14:102929544 (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 c.138_162+20del Likely pathogenic ★★ same condition
AMN c.208-13_211del Likely pathogenic ★★ same condition
AMN c.844-14_845del Likely pathogenic ★★ same condition
AMN p.Gly5fs Pathogenic/Likely pathogenic ★★ same condition
AMN c.513+2del Likely pathogenic ★ same condition
AMN p.Arg323fs Pathogenic ★ same condition
AMN p.Asn27fs Pathogenic ★ same condition
AMN p.Gln12fs 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-760-plus-12del (accessed [today's date]).

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