Is AMN p.Ser57fs (c.168_169dup) pathogenic?

AMN p.Ser57fs (c.168169dup) is classified Likely pathogenic in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-19). Absent from gnomAD.

How common is AMN p.Ser57fs (c.168_169dup) in the general population?

AMN p.Ser57fs (c.168_169dup) is absent from gnomAD (gnomAD).

AMN p.Ser57fs

c.168_169dup · rs1555380625 · VCV419161

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.5	GERP -0.026, 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.Ser57fs
Coding: c.168_169dup
MANE Select: NM_030943
dbSNP: rs1555380625
Type: Microsatellite
Location: chr14:102923937 (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 57: a β-strand; a disulfide bond

Full AMN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMN p.Ser57Ter Pathogenic ★ same residue
AMN c.44-7_44-5del Uncertain significance ★★ same type
AMN p.Asp108fs Pathogenic ★ same type
AMN p.His438fs 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-ser57fs (accessed [today's date]).

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