Is AMN p.His285= (c.855C>T) pathogenic?

AMN p.His285= (c.855C>T) is classified Likely benign in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-18). Ultra-rare (popmax 0.0334%, mid); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with AMN p.His285= (c.855C>T)?

AMN p.His285= (c.855C>T) is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN p.His285= (c.855C>T) in the general population?

AMN p.His285= (c.855C>T) is ultra-rare (popmax 0.0334%, mid) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

AMN p.His285=

c.855C>T · rs369865835 · VCV2983793

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57	GERP -1.9, phastCons 0.32
Overall
CADD	14.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% Middle Eastern · 2/5,994 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.000641% 10/1,559,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0334%	2,997
Admixed American	0.0038%	26,332
Remaining individualsnot grpmax-eligible	0.00165%	60,440
African / African-American	0.00136%	73,346
South Asian	0.00118%	84,578
European (non-Finnish)	0.00026%	384,304

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.His285=
Coding: c.855C>T
MANE Select: NM_030943
dbSNP: rs369865835
Type: single nucleotide variant
Location: chr14:102929935 (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 p.His285Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
AMN p.His285Leu Uncertain significance ★ ⚠ same residue
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

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-his285 (accessed [today's date]).

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