Is AMN p.Ala362= (c.1086G>A) pathogenic?

AMN p.Ala362= (c.1086G>A) is classified Likely benign in AMN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-01). Ultra-rare (popmax 0.047%, nfe); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with AMN p.Ala362= (c.1086G>A)?

AMN p.Ala362= (c.1086G>A) is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN p.Ala362= (c.1086G>A) in the general population?

AMN p.Ala362= (c.1086G>A) is ultra-rare (popmax 0.047%, nfe) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

AMN p.Ala362=

c.1086G>A · rs959195796 · VCV617973

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.047%, nfe)

Conditions

Imerslund-Grasbeck syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.04	GERP -1.4
Overall
CADD	9.758	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.047% European (non-Finnish) · 503/1,070,634 alleles

Filtering AF 0.0435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0422%

Overall 0.038% 525/1,382,680 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.047%	2,128
Remaining individualsnot grpmax-eligible	0.0324%	3,083
African / African-American	0.00604%	16,552
Admixed American	0.00298%	33,610

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.Ala362=
Coding: c.1086G>A
dbSNP: rs959195796
Type: single nucleotide variant
Location: chr14:102930244 (GRCh38)

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)

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-ala362 (accessed [today's date]).

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