Is AGMO p.Leu439fs (c.1314dup) pathogenic?

AGMO p.Leu439fs (c.1314dup) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). Ultra-rare (popmax 0.0501%, amr).

How common is AGMO p.Leu439fs (c.1314dup) in the general population?

AGMO p.Leu439fs (c.1314dup) is ultra-rare (popmax 0.0501%, amr) (gnomAD).

AGMO p.Leu439fs

c.1314dup · VCV4074314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0501%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (13 of 13) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 1.9, phastCons 1
Overall
CADD	27.4	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 0.0501% Admixed American · 30/59,940 alleles

Filtering AF 0.036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.012% 194/1,612,554 alleles · ultra-rare exomes 173/1,460,406 · genomes 21/152,148 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0501%	1,998
Remaining individualsnot grpmax-eligible	0.0288%	3,468
European (non-Finnish)	0.0124%	8,077

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: AGMO
Protein: p.Leu439fs
Coding: c.1314dup
MANE Select: NM_001004320
Type: Duplication
Location: chr7:15201308 (GRCh38)
Gene constraint: LOEUF 1.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90

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

Similar variants

AGMO p.Tyr21fs Benign ★★ same type
AGMO c.1263+1dup Uncertain significance ★ same type
AGMO p.Gly307_Lys308insTer Uncertain significance ★ same type
AGMO p.Trp282fs Uncertain significance ★ same type
AGMO c.823-12dup Benign ★ same type
AGMO p.Phe295fs 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/agmo-p-leu439fs (accessed [today's date]).

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