Is AGA p.Pro268fs (c.800dup) pathogenic?

AGA p.Pro268fs (c.800dup) is classified Pathogenic/Likely pathogenic in AGA (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-10-02). Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with AGA p.Pro268fs (c.800dup)?

AGA p.Pro268fs (c.800dup) is associated with Inborn genetic diseases, aspartylglucosaminuria (ClinVar).

How common is AGA p.Pro268fs (c.800dup) in the general population?

AGA p.Pro268fs (c.800dup) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

AGA p.Pro268fs

c.800dup · rs386833436 · VCV225

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

Inborn genetic diseases

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 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.7	GERP -2.9
Overall
CADD	32.0	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 0.0117% Admixed American · 7/60,008 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000434% 7/1,613,674 alleles · ultra-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: AGA
Protein: p.Pro268fs
Coding: c.800dup
MANE Select: NM_000027
dbSNP: rs386833436
Type: Duplication
Location: chr4:177434387 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.41 · 2 PDB
Residue 268: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: aspartylglucosaminuria

Similar variants

AGA p.Met63fs Pathogenic ★★ same condition
AGA c.394+10dup Benign/Likely benign ★★ same condition
AGA p.Asn170fs Pathogenic ★ same condition
AGA p.Asp174fs Pathogenic ★ same condition
AGA p.Ile240fs Likely pathogenic ★ same condition
AGA p.Leu267fs Pathogenic ★ same condition
AGA p.Met90fs Pathogenic ★ same condition
AGA p.Pro28fs Likely pathogenic ★ same condition

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/aga-p-pro268fs (accessed [today's date]).

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