Is AMN p.Asp108fs (c.320_321dup) pathogenic?

AMN p.Asp108fs (c.320321dup) is classified Pathogenic in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2017-01-01). Absent from gnomAD; Associated with vitamin B12 deficiency.

What condition is associated with AMN p.Asp108fs (c.320_321dup)?

AMN p.Asp108fs (c.320_321dup) is associated with vitamin B12 deficiency, megaloblastic anemia (ClinVar).

How common is AMN p.Asp108fs (c.320_321dup) in the general population?

AMN p.Asp108fs (c.320_321dup) is absent from gnomAD (gnomAD).

AMN p.Asp108fs

c.320_321dup · rs1555381324 · VCV523538

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

vitamin B12 deficiency

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 10	GERP 1.2, 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.Asp108fs
Coding: c.320_321dup
MANE Select: NM_030943
dbSNP: rs1555381324
Type: Microsatellite
Location: chr14:102928779 (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

vitamin B12 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: megaloblastic anemia

Similar variants

AMN p.Asp108= Benign/Likely benign ★★ same residue
AMN p.Phe50Ser Uncertain significance ★★ ⚠ same condition
AMN c.44-7_44-5del Uncertain significance ★★ same type
AMN p.His438fs Likely pathogenic ★ same type
AMN p.Ser57fs Likely pathogenic ★ same type
AMN p.Gly46del Uncertain significance ★ same type
AMN p.Ser292fs Uncertain significance ★ same type
AMN p.450EA[3] Likely benign ★ same type

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-asp108fs (accessed [today's date]).

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