Is AMN c.843+12G>A pathogenic?

AMN c.843+12G>A is classified Benign/Likely benign in AMN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Rare (popmax 0.422%, nfe); Associated with Imerslund-Grasbeck syndrome type 2.

What condition is associated with AMN c.843+12G>A?

AMN c.843+12G>A is associated with Imerslund-Grasbeck syndrome type 2, Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN c.843+12G>A in the general population?

AMN c.843+12G>A is rare (popmax 0.422%, nfe) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

AMN c.843+12G>A

rs140902778 · VCV1617679

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.422%, nfe)

Conditions

Imerslund-Grasbeck syndrome type 2

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -2, phastCons 0.003
Overall
CADD	11.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.422% European (non-Finnish) · 4,840/1,146,834 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.408%

Overall 0.35% 5,430/1,549,482 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.422%	237
Admixed American	0.337%	297
Remaining individualsnot grpmax-eligible	0.303%	330
Middle Eastern	0.191%	524
Finnishnot grpmax-eligible	0.174%	575
African / African-American	0.0765%	1,306
South Asian	0.075%	1,333
Ashkenazi Jewishnot grpmax-eligible	0.0175%	5,728

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.843+12G>A
MANE Select: NM_030943
dbSNP: rs140902778
Type: single nucleotide variant
Location: chr14:102929749 (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

Also linked: Imerslund-Grasbeck syndrome

For Imerslund-Gräsbeck syndrome (Orphanet):

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

Similar variants

AMN c.208-1G>C Pathogenic/Likely pathogenic ★★ same condition
AMN c.296-1G>A Likely pathogenic ★★ same condition
AMN c.44-1G>A Likely pathogenic ★★ same condition
AMN c.760+1G>A Likely pathogenic ★★ same condition
AMN c.844-1G>C Likely pathogenic ★★ same condition
AMN p.Thr41Ile Likely pathogenic ★★ ⚠ same condition
AMN p.Trp391Ter Pathogenic/Likely pathogenic ★★ same condition
AMN c.296-3C>T 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/amn-c-843-plus-12g-a (accessed [today's date]).

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