Is AMN p.Ser292fs (c.873_874dup) pathogenic?

AMN p.Ser292fs (c.873874dup) is classified Uncertain significance in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-21). Very rare (popmax 0.000173%, nfe); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with AMN p.Ser292fs (c.873_874dup)?

AMN p.Ser292fs (c.873_874dup) is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN p.Ser292fs (c.873_874dup) in the general population?

AMN p.Ser292fs (c.873_874dup) is very rare (popmax 0.000173%, nfe) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

AMN p.Ser292fs

c.873_874dup · rs2139311797 · VCV1061221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000173%, nfe)

Conditions

Imerslund-Grasbeck syndrome

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 9 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2	GERP -1.9

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000173% European (non-Finnish) · 2/1,154,838 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000142% 2/1,411,142 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
Protein: p.Ser292fs
Coding: c.873_874dup
MANE Select: NM_030943
dbSNP: rs2139311797
Type: Microsatellite
Location: chr14:102929950 (GRCh38)
Gene constraint: LOEUF 1.446 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.78 · 1 PDB
Residue 292: a β-strand

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.44-7_44-5del Uncertain significance ★★ same condition
AMN p.His438fs Likely pathogenic ★ same condition
AMN p.450EA[3] Likely benign ★ same condition
AMN c.138_162+20del Likely pathogenic ★★ same condition
AMN c.208-13_211del Likely pathogenic ★★ same condition
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

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-ser292fs (accessed [today's date]).

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