Is AUH p.Phe157fs (c.471del) pathogenic?

AUH p.Phe157fs (c.471del) is classified Pathogenic in AUH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). Very rare (popmax 8.48e-05%, nfe); Associated with 3-methylglutaconic aciduria type 1.

What condition is associated with AUH p.Phe157fs (c.471del)?

AUH p.Phe157fs (c.471del) is associated with 3-methylglutaconic aciduria type 1 (ClinVar).

How common is AUH p.Phe157fs (c.471del) in the general population?

AUH p.Phe157fs (c.471del) is very rare (popmax 8.48e-05%, nfe) (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.Phe157fs

c.471del · rs2538069355 · VCV2812871

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP 2.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,866 alleles

Overall 6.84e-05% 1/1,461,590 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.Phe157fs
Coding: c.471del
MANE Select: NM_001698
dbSNP: rs2538069355
Type: Deletion
Location: chr9:91325352 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63 · 3 PDB
Residue 157: an α-helix

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.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
AUH c.943-6del 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-phe157fs (accessed [today's date]).

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