Is AGMO p.Trp282fs (c.842dup) pathogenic?

AGMO p.Trp282fs (c.842dup) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). Ultra-rare (popmax 0.0402%, nfe).

How common is AGMO p.Trp282fs (c.842dup) in the general population?

AGMO p.Trp282fs (c.842dup) is ultra-rare (popmax 0.0402%, nfe) (gnomAD).

AGMO p.Trp282fs

c.842dup · rs759729273 · VCV2577601

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 0.0402%, nfe)

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 9 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.23	GERP -4.8, phastCons 0.5
Overall
CADD	34.0	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 0.0402% European (non-Finnish) · 474/1,179,368 alleles

Filtering AF 0.0371% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.036%

Overall 0.0314% 506/1,611,784 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0402%	2,488
Finnishnot grpmax-eligible	0.025%	3,999
Remaining individualsnot grpmax-eligible	0.0176%	5,672
African / African-American	0.00404%	24,749
Admixed American	0.00335%	29,827

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.Trp282fs
Coding: c.842dup
MANE Select: NM_001004320
dbSNP: rs759729273
Type: Duplication
Location: chr7:15387520 (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.Leu439fs 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-trp282fs (accessed [today's date]).

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