Is AMN p.450EA[3] (c.1348GAGGCC[3]) pathogenic?

AMN p.450EA[3] (c.1348GAGGCC[3]) is classified Likely benign in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). Rare (popmax 0.157%, mid); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with AMN p.450EA[3] (c.1348GAGGCC[3])?

AMN p.450EA[3] (c.1348GAGGCC[3]) is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN p.450EA[3] (c.1348GAGGCC[3]) in the general population?

AMN p.450EA[3] (c.1348GAGGCC[3]) is rare (popmax 0.157%, mid) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

AMN p.450EA[3]

c.1348GAGGCC[3] · rs763564473 · VCV698419

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.157%, mid)

Conditions

Imerslund-Grasbeck syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.043	GERP -1.5, phastCons 0.18
Overall
CADD	1.851	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.157% Middle Eastern · 9/5,722 alleles

Filtering AF 0.082% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0612%

Overall 0.0279% 445/1,595,034 alleles · rare exomes 404/1,442,682 · genomes 41/152,352 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.373%	268
Middle Easterngrpmax	0.157%	636
Remaining individualsnot grpmax-eligible	0.06%	1,666
South Asian	0.0385%	2,594
Admixed American	0.0242%	4,135
European (non-Finnish)	0.0195%	5,119
African / African-American	0.0161%	6,221
Finnishnot grpmax-eligible	0.00165%	60,704

Ashkenazi Jewish 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
Protein: p.450EA[3]
Coding: c.1348GAGGCC[3]
MANE Select: NM_030943
dbSNP: rs763564473
Type: Microsatellite
Location: chr14:102930661 (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

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AMN p.Ser292fs Uncertain significance ★ 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-450ea-3 (accessed [today's date]).

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