Is GCDH p.Ser157= (c.471C>T) pathogenic?

GCDH p.Ser157= (c.471C>T) is classified Conflicting classifications of pathogenicity in GCDH (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-28). Rare (popmax 0.269%, afr); Associated with Inborn genetic diseases.

What condition is associated with GCDH p.Ser157= (c.471C>T)?

GCDH p.Ser157= (c.471C>T) is associated with Inborn genetic diseases, glutaryl-CoA dehydrogenase deficiency (ClinVar).

How common is GCDH p.Ser157= (c.471C>T) in the general population?

GCDH p.Ser157= (c.471C>T) is rare (popmax 0.269%, afr) (gnomAD).

GCDH p.Ser157=

c.471C>T · rs146682905 · VCV328329

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.269%, afr)

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 -8.9	GERP -3.1
Overall
CADD	3.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.269% African / African-American · 202/75,000 alleles

Filtering AF 0.239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.227%

Overall 0.0193% 312/1,614,010 alleles · rare exomes 194/1,461,792 · genomes 118/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.269%	371
Middle Eastern	0.033%	3,031
Admixed American	0.0133%	7,502
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.00763%	13,111
East Asian	0.00223%	44,866
South Asian	0.0011%	91,076

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.Ser157=
Coding: c.471C>T
MANE Select: NM_000159
dbSNP: rs146682905
Type: single nucleotide variant
Location: chr19:12893619 (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.Ser157Arg Uncertain significance ★ ⚠ same residue
GCDH p.Ser157_Glu158delinsArg 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

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-ser157 (accessed [today's date]).

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