GCDH p.Pro364=
c.1092C>T · rs146363703 · VCV758333
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.4 | GERP -2.9 |
| Overall | ||
| CADD | 0.049 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00465%
75/1,614,118 alleles · ultra-rare
exomes 66/1,461,874 · genomes 9/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| South Asian | 0.0165% | 6,072 |
| East Asian | 0.0134% | 7,481 |
| African / African-American | 0.00667% | 15,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| European (non-Finnish) | 0.00347% | 28,781 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Admixed American | 0.00167% | 60,014 |
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.Pro364=
- Coding
- c.1092C>T
- MANE Select
- NM_000159
- dbSNP
- rs146363703
- Type
- single nucleotide variant
- Location
- chr19:12897712 (GRCh38)
- Gene constraint
- LOEUF 0.752 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.23 · 4 PDB
- Residue 364
- an α-helix
Similar variants
- 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
- GCDH c.505+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-pro364 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown