Is AUH p.Ser27fs (c.80del) pathogenic?

AUH p.Ser27fs (c.80del) is classified Pathogenic in AUH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2010-09-21). Very rare (popmax 0.000658%); Associated with 3-methylglutaconic aciduria type 1.

What condition is associated with AUH p.Ser27fs (c.80del)?

AUH p.Ser27fs (c.80del) is associated with 3-methylglutaconic aciduria type 1 (ClinVar).

How common is AUH p.Ser27fs (c.80del) in the general population?

AUH p.Ser27fs (c.80del) is very rare (popmax 0.000658%) (gnomAD).

How is 3-methylglutaconic aciduria type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AUH p.Ser27fs

c.80del · rs730880310 · VCV9058

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000658%)

Conditions

3-methylglutaconic aciduria type 1

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 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.2	GERP -2.5
Overall
CADD	19.48	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 0.000658%

Overall 0.000658% 1/151,988 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: AUH
Protein: p.Ser27fs
Coding: c.80del
MANE Select: NM_001698
dbSNP: rs730880310
Type: Deletion
Location: chr9:91361810 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63 · 3 PDB

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

Disease context

3-methylglutaconic aciduria type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 3-methylglutaconic aciduria type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

AUH c.656-2_656-1del Likely pathogenic ★★ same condition
AUH c.656-2del Likely pathogenic ★ same condition
AUH p.Phe157fs Pathogenic ★ same condition
AUH p.Pro32fs Pathogenic ★ same condition
AUH c.263-5_263-2del Conflicting classifications of pathogenicity ★ same condition
AUH p.Val90_Ile94del Uncertain significance ★ same condition
AUH c.598+9_598+12del Likely benign ★ same condition
AUH c.895-9del Benign ★ 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/auh-p-ser27fs (accessed [today's date]).

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