Is AUH c.655+3A>C pathogenic?

AUH c.655+3A>C is classified Uncertain significance in AUH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-22). Very rare (popmax 0.00667%, amr); Associated with 3-methylglutaconic aciduria type 1.

What condition is associated with AUH c.655+3A>C?

AUH c.655+3A>C is associated with 3-methylglutaconic aciduria type 1 (ClinVar).

How common is AUH c.655+3A>C in the general population?

AUH c.655+3A>C is very rare (popmax 0.00667%, amr) (gnomAD).

How is 3-methylglutaconic aciduria type 1 inherited?

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

AUH c.655+3A>C

rs755914350 · VCV287536

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

3-methylglutaconic aciduria type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +3	donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	Δ0.90	donor loss, 3 bp away · masked 0 · deltas
Pangolin	Δ0.69	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Non-coding constraint	Z -1.22	1 kb window · o/e 1.10 · regional · uncalibrated
Overall
CADD	14.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,004 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00415% 67/1,613,904 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,001
European (non-Finnish)	0.00492%	20,344
African / African-American	0.004%	24,974
Remaining individualsnot grpmax-eligible	0.0032%	31,239

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
Coding: c.655+3A>C
MANE Select: NM_001698
dbSNP: rs755914350
Type: single nucleotide variant
Location: chr9:91296018 (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.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 p.Ala117Val Uncertain significance ★★ ⚠ same condition
AUH p.Ala227Thr Uncertain significance ★★ ⚠ same condition
AUH p.Ala8Val Uncertain significance ★★ same condition
AUH p.Arg125Gln 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-c-655-plus-3a-c (accessed [today's date]).

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