Is GCDH p.Phe287= (c.861C>T) pathogenic?

GCDH p.Phe287= (c.861C>T) is classified Likely benign in GCDH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-07). Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with GCDH p.Phe287= (c.861C>T)?

GCDH p.Phe287= (c.861C>T) is associated with Inborn genetic diseases, glutaryl-CoA dehydrogenase deficiency (ClinVar).

How common is GCDH p.Phe287= (c.861C>T) in the general population?

GCDH p.Phe287= (c.861C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

GCDH p.Phe287=

c.861C>T · rs200757991 · VCV736544

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.9	GERP -3.2
Overall
CADD	3.785	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00477% 77/1,612,732 alleles · ultra-rare exomes 65/1,460,544 · genomes 12/152,188 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Admixed American	0.0283%	3,528
South Asian	0.00769%	13,010
Remaining individualsnot grpmax-eligible	0.0048%	20,817
European (non-Finnish)	0.00398%	25,097
Finnishnot grpmax-eligible	0.00158%	63,284

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.Phe287=
Coding: c.861C>T
MANE Select: NM_000159
dbSNP: rs200757991
Type: single nucleotide variant
Location: chr19:12896918 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.23 · 4 PDB
Residue 287: an α-helix; a binding site

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.Phe287Ser 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-phe287 (accessed [today's date]).

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