Is GCDH p.Ala41= (c.123T>C) pathogenic?

GCDH p.Ala41= (c.123T>C) is classified Likely benign in GCDH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-25). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GCDH p.Ala41= (c.123T>C)?

GCDH p.Ala41= (c.123T>C) is associated with Inborn genetic diseases, glutaryl-CoA dehydrogenase deficiency (ClinVar).

How common is GCDH p.Ala41= (c.123T>C) in the general population?

GCDH p.Ala41= (c.123T>C) is absent from gnomAD v4.1 (gnomAD).

GCDH p.Ala41=

c.123T>C · rs2145938906 · VCV1609780

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP 0.26, phastCons 0.11
Overall
CADD	11.66	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.Ala41=
Coding: c.123T>C
MANE Select: NM_000159
dbSNP: rs2145938906
Type: single nucleotide variant
Location: chr19:12891518 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.23 · 4 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glutaryl-CoA dehydrogenase deficiency

Similar variants

GCDH p.Ala41Val 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
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-ala41 (accessed [today's date]).

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