Is GCDH p.Arg313Trp (c.937C>T) pathogenic?

GCDH p.Arg313Trp (c.937C>T) is classified Pathogenic/Likely pathogenic in GCDH (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-06-11). AlphaMissense: likely benign (0.3232); Very rare (popmax 0.00878%, sas); Associated with glutaryl-CoA dehydrogenase deficiency.

What condition is associated with GCDH p.Arg313Trp (c.937C>T)?

GCDH p.Arg313Trp (c.937C>T) is associated with glutaryl-CoA dehydrogenase deficiency (ClinVar).

How common is GCDH p.Arg313Trp (c.937C>T) in the general population?

GCDH p.Arg313Trp (c.937C>T) is very rare (popmax 0.00878%, sas) (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.Arg313Trp (c.937C>T)?

AlphaMissense predicts likely benign (score 0.3232) — an in-silico prediction, not a clinical call.

GCDH p.Arg313Trp

c.937C>T · rs779315456 · VCV379529

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.3232 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glutaryl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.3232	likely benign ⚠ discordant with ClinVar
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -14.78	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 8,233 bp · p 0.00042 · regional, not allelic
Overall
CADD	28.6	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

Grpmax group 0.00878% South Asian · 8/91,080 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.000992% 16/1,612,172 alleles · very rare exomes 13/1,459,964 · genomes 3/152,208 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,385
Finnishnot grpmax-eligible	0.0016%	62,654
European (non-Finnish)	0.000593%	168,510

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: GCDH
Protein: p.Arg313Trp
Coding: c.937C>T
MANE Select: NM_000159
dbSNP: rs779315456
Type: single nucleotide variant
Location: chr19:12896994 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.23 · 4 PDB
Residue 313: an α-helix; a UniProt-annotated variant site (in ga1)

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.Arg313Gln Pathogenic/Likely 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
GCDH c.271+1G>A Pathogenic ★★ same condition
GCDH c.334+1G>A 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-arg313trp (accessed [today's date]).

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