Is GCDH p.Arg402Pro (c.1205G>C) pathogenic?

GCDH p.Arg402Pro (c.1205G>C) is classified Conflicting classifications of pathogenicity in GCDH (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.9787); Absent from gnomAD v4.1; Associated with glutaryl-CoA dehydrogenase deficiency.

What condition is associated with GCDH p.Arg402Pro (c.1205G>C)?

GCDH p.Arg402Pro (c.1205G>C) is associated with glutaryl-CoA dehydrogenase deficiency (ClinVar).

How common is GCDH p.Arg402Pro (c.1205G>C) in the general population?

GCDH p.Arg402Pro (c.1205G>C) 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.

What do computational predictors say about GCDH p.Arg402Pro (c.1205G>C)?

AlphaMissense predicts likely pathogenic (score 0.9787) — an in-silico prediction, not a clinical call.

GCDH p.Arg402Pro

c.1205G>C · rs786204626 · VCV3233788

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9787 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glutaryl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.9787	likely pathogenic · top 2% in GCDH
REVEL	0.976	strongly pathogenic-leaning
SaProt	LLR -17.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 8,233 bp · p 0.00042 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Arg402Pro
Coding: c.1205G>C
MANE Select: NM_000159
dbSNP: rs786204626
Type: single nucleotide variant
Location: chr19:12897825 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.23 · 4 PDB
Residue 402: an α-helix; a UniProt-annotated variant site (in ga1); a UniProt-annotated variant site (in ga1; most common mutation identified; loss of tetramerization; loss enzyme activity)

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.Arg402Gln Pathogenic/Likely pathogenic ★★ same residue
GCDH p.Arg402Trp Pathogenic/Likely pathogenic ★★ same residue
GCDH p.Arg402Gly Pathogenic ★ 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-arg402pro (accessed [today's date]).

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