Is GCDH p.Arg82= (c.246C>A) pathogenic?

GCDH p.Arg82= (c.246C>A) is classified Likely benign in GCDH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Absent from gnomAD v4.1; Associated with glutaryl-CoA dehydrogenase deficiency.

What condition is associated with GCDH p.Arg82= (c.246C>A)?

GCDH p.Arg82= (c.246C>A) is associated with glutaryl-CoA dehydrogenase deficiency (ClinVar).

How common is GCDH p.Arg82= (c.246C>A) in the general population?

GCDH p.Arg82= (c.246C>A) is absent from gnomAD v4.1 (gnomAD).

How is Glutaryl-CoA dehydrogenase deficiency inherited?

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

GCDH p.Arg82=

c.246C>A · rs1466044796 · VCV1652118

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

glutaryl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.05	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.4	GERP -3
Overall
CADD	7.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GCDH
Protein: p.Arg82=
Coding: c.246C>A
MANE Select: NM_000159
dbSNP: rs1466044796
Type: single nucleotide variant
Location: chr19:12891949 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.23 · 4 PDB
Residue 82: an α-helix

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

Disease context

glutaryl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glutaryl-CoA dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: >1 / 1000 (Specific population)

Similar variants

GCDH p.Arg82Cys Likely pathogenic ★ ⚠ same residue
GCDH p.Arg82Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
GCDH p.Arg82Gly Uncertain significance ★ ⚠ same residue
GCDH c.1082+2T>C Pathogenic/Likely pathogenic ★★ same condition
GCDH c.1243+1G>T Pathogenic ★★ same condition
GCDH c.1244-2A>C Pathogenic ★★ same condition
GCDH c.127+1G>A Pathogenic ★★ same condition
GCDH c.127+1G>T Pathogenic/Likely pathogenic ★★ 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/gcdh-p-arg82 (accessed [today's date]).

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