Is GCDH p.Phe177= (c.531C>T) pathogenic?

GCDH p.Phe177= (c.531C>T) is classified Likely benign in GCDH (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Rare (popmax 0.126%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GCDH p.Phe177= (c.531C>T)?

GCDH p.Phe177= (c.531C>T) is associated with Inborn genetic diseases, glutaryl-CoA dehydrogenase deficiency (ClinVar).

How common is GCDH p.Phe177= (c.531C>T) in the general population?

GCDH p.Phe177= (c.531C>T) is rare (popmax 0.126%, nfe) (gnomAD).

GCDH p.Phe177=

c.531C>T · rs144013229 · VCV385460

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.126%, nfe)

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 -6.5	GERP -2.8
Overall
CADD	2.976	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.126% European (non-Finnish) · 1,489/1,179,936 alleles

Filtering AF 0.121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.119%

Overall 0.0956% 1,543/1,613,986 alleles · rare exomes 1,488/1,461,792 · genomes 55/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.126%	792
Remaining individualsnot grpmax-eligible	0.0352%	2,841
African / African-American	0.0187%	5,358
Finnishnot grpmax-eligible	0.0125%	8,000
South Asian	0.00769%	13,011
Admixed American	0.005%	20,003

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.Phe177=
Coding: c.531C>T
MANE Select: NM_000159
dbSNP: rs144013229
Type: single nucleotide variant
Location: chr19:12896017 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.23 · 4 PDB
Residue 177: a binding site; a β-strand

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.Phe177Leu 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-phe177 (accessed [today's date]).

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