Is AUH p.Pro317= (c.951A>T) pathogenic?

AUH p.Pro317= (c.951A>T) is classified Conflicting classifications of pathogenicity in AUH (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-10). Rare (popmax 0.171%, sas); Associated with 3-methylglutaconic aciduria type 1.

What condition is associated with AUH p.Pro317= (c.951A>T)?

AUH p.Pro317= (c.951A>T) is associated with 3-methylglutaconic aciduria type 1 (ClinVar).

How common is AUH p.Pro317= (c.951A>T) in the general population?

AUH p.Pro317= (c.951A>T) is rare (popmax 0.171%, sas) (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.Pro317=

c.951A>T · rs530710210 · VCV367476

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.171%, sas)

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 1.1	GERP -0.56, phastCons 1
Overall
CADD	8.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.171% South Asian · 155/90,456 alleles

Filtering AF 0.149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.141%

Overall 0.0106% 170/1,607,680 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.171%	584
Middle Eastern	0.0496%	2,017
Remaining individualsnot grpmax-eligible	0.0177%	5,657
European (non-Finnish)	8.5e-05%	1,176,671

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.Pro317=
Coding: c.951A>T
MANE Select: NM_001698
dbSNP: rs530710210
Type: single nucleotide variant
Location: chr9:91214417 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63 · 3 PDB
Residue 317: a turn

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.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
AUH p.Ala8Val 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-pro317 (accessed [today's date]).

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