Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 10 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.16%, eas)
Conditions
2
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 -10 | GERP -2.9 |
| Overall | ||
| CADD | 0.148 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.16%
East Asian · 1,417/44,870 alleles
Filtering AF
3.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.97%
Overall
0.109%
1,751/1,613,784 alleles · low-frequency
exomes 1,544/1,461,568 · genomes 207/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 3.16% | 32 |
| Remaining individualsnot grpmax-eligible | 0.189% | 530 |
| South Asian | 0.156% | 641 |
| Admixed American | 0.0267% | 3,750 |
| African / African-American | 0.024% | 4,168 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.00331% | 30,256 |
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.Ala337=
- Coding
- c.1011A>G
- MANE Select
- NM_000159
- dbSNP
- rs2229460
- Type
- single nucleotide variant
- Location
- chr19:12897357 (GRCh38)
- Gene constraint
- LOEUF 0.752 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.23 · 4 PDB
- Residue 337
- 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-ala337 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown