Is AMN p.Ser165fs (c.493dup) pathogenic?

AMN p.Ser165fs (c.493dup) is classified Pathogenic in AMN (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with Imerslund-Grasbeck syndrome type 2.

What condition is associated with AMN p.Ser165fs (c.493dup)?

AMN p.Ser165fs (c.493dup) is associated with Imerslund-Grasbeck syndrome type 2 (ClinVar).

How common is AMN p.Ser165fs (c.493dup) in the general population?

AMN p.Ser165fs (c.493dup) is absent from gnomAD (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

AMN p.Ser165fs

c.493dup · rs2542695969 · VCV1879782

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Imerslund-Grasbeck syndrome type 2

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 5 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP 0.049, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AMN
Protein: p.Ser165fs
Coding: c.493dup
MANE Select: NM_030943
dbSNP: rs2542695969
Type: Duplication
Location: chr14:102928954 (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 165: a disulfide bond; a β-strand

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

For Imerslund-Gräsbeck syndrome (Orphanet):

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

Similar variants

AMN p.Ser349fs Likely pathogenic ★★ same condition
AMN p.Ala372_Leu374dup Uncertain significance ★★ same condition
AMN p.Val378_Ala379insLeuLeuVal Uncertain significance ★★ same condition
AMN p.Val442fs Uncertain significance ★★ same condition
AMN c.1257+20dup Benign/Likely benign ★★ same condition
AMN p.Gly448_Ala449dup Benign ★★ same condition
AMN p.Glu76fs Likely pathogenic ★ same condition
AMN c.761-15dup 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-p-ser165fs (accessed [today's date]).

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