Is AMN p.Ter454Arg (c.1360T>A) pathogenic?

AMN p.Ter454Arg (c.1360T>A) is classified Uncertain significance in AMN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). Very rare (popmax 8.59e-05%, nfe).

How common is AMN p.Ter454Arg (c.1360T>A) in the general population?

AMN p.Ter454Arg (c.1360T>A) is very rare (popmax 8.59e-05%, nfe) (gnomAD).

AMN p.Ter454Arg

c.1360T>A · rs1566829872 · VCV591680

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.59e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.058, phastCons 1
Overall
CADD	15.82	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.59e-05% European (non-Finnish) · 1/1,164,006 alleles

Overall 7e-05% 1/1,428,124 alleles · very rare

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.Ter454Arg
Coding: c.1360T>A
MANE Select: NM_030943
dbSNP: rs1566829872
Type: single nucleotide variant
Location: chr14:102930678 (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

Similar variants

AMN c.208-1G>C Pathogenic/Likely pathogenic ★★ same type
AMN c.296-1G>A Likely pathogenic ★★ same type
AMN c.44-1G>A Likely pathogenic ★★ same type
AMN c.760+1G>A Likely pathogenic ★★ same type
AMN c.844-1G>C Likely pathogenic ★★ same type
AMN p.Thr41Ile Likely pathogenic ★★ ⚠ same type
AMN p.Trp391Ter Pathogenic/Likely pathogenic ★★ same type
AMN c.296-3C>T Uncertain significance ★★ 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-ter454arg (accessed [today's date]).

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