Is AUH p.Ser39= (c.117G>C) pathogenic?

AUH p.Ser39= (c.117G>C) is classified Likely benign in AUH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). Very rare (popmax 0.00693%, afr); Associated with 3-methylglutaconic aciduria type 1.

What condition is associated with AUH p.Ser39= (c.117G>C)?

AUH p.Ser39= (c.117G>C) is associated with 3-methylglutaconic aciduria type 1 (ClinVar).

How common is AUH p.Ser39= (c.117G>C) in the general population?

AUH p.Ser39= (c.117G>C) is very rare (popmax 0.00693%, afr) (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.Ser39=

c.117G>C · rs759828827 · VCV761836

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00693%, afr)

Conditions

3-methylglutaconic aciduria type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.38	GERP -2.5
Overall
CADD	5.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00693% African / African-American · 5/72,170 alleles

Filtering AF 0.00272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00177%

Overall 0.00168% 26/1,544,234 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00693%	14,434
Admixed American	0.00591%	16,933
Remaining individualsnot grpmax-eligible	0.00167%	59,882
European (non-Finnish)	0.00148%	67,402

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.Ser39=
Coding: c.117G>C
MANE Select: NM_001698
dbSNP: rs759828827
Type: single nucleotide variant
Location: chr9:91361773 (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 p.Ser39Leu Uncertain significance ★ ⚠ same residue
AUH c.505+1G>C Pathogenic/Likely pathogenic ★★ same condition
AUH p.Ala240Val Likely pathogenic ★★ same condition
AUH p.Arg197Ter Pathogenic ★★ same condition
AUH p.Arg241Ter Pathogenic/Likely pathogenic ★★ same condition
AUH c.655+3A>C Uncertain significance ★★ same condition
AUH p.Ala117Val Uncertain significance ★★ ⚠ same condition
AUH p.Ala227Thr Uncertain significance ★★ ⚠ 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-ser39 (accessed [today's date]).

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