Is GCDH p.Arg88Ser (c.262C>A) pathogenic?

GCDH p.Arg88Ser (c.262C>A) is classified Pathogenic/Likely pathogenic in GCDH (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-05-29). AlphaMissense: likely pathogenic (0.9054); Very rare (popmax 0.00534%, nfe); Associated with glutaryl-CoA dehydrogenase deficiency.

What condition is associated with GCDH p.Arg88Ser (c.262C>A)?

GCDH p.Arg88Ser (c.262C>A) is associated with glutaryl-CoA dehydrogenase deficiency (ClinVar).

How common is GCDH p.Arg88Ser (c.262C>A) in the general population?

GCDH p.Arg88Ser (c.262C>A) is very rare (popmax 0.00534%, nfe) (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.Arg88Ser (c.262C>A)?

AlphaMissense predicts likely pathogenic (score 0.9054) — an in-silico prediction, not a clinical call.

GCDH p.Arg88Ser

c.262C>A · rs142967670 · VCV529444

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9054 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glutaryl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.9054	likely pathogenic ✓ concordant with ClinVar
REVEL	0.92	moderately pathogenic-leaning
SaProt	LLR -14.62	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 4.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 8,233 bp · p 0.00042 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 0.00534% European (non-Finnish) · 63/1,180,050 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.0039% 63/1,614,102 alleles · very rare exomes 62/1,461,892 · genomes 1/152,210 · joint denominator

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.Arg88Ser
Coding: c.262C>A
MANE Select: NM_000159
dbSNP: rs142967670
Type: single nucleotide variant
Location: chr19:12891965 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.23 · 4 PDB
Residue 88: a UniProt-annotated variant site (in ga1); 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.Arg88Cys Pathogenic ★★ same residue
GCDH p.Arg88Gly Likely pathogenic ★★ same residue
GCDH p.Arg88His Pathogenic/Likely pathogenic ★★ ⚠ same residue
GCDH p.Arg88Pro 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

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-arg88ser (accessed [today's date]).

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