HADH p.Phe217=
c.651T>C · rs756177386 · VCV2195201
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, sas)
Conditions
1
3-hydroxyacyl-CoA dehydrogenase deficiency
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 -0.43 | GERP -5.1, phastCons 0.012 |
| Overall | ||
| CADD | 2.902 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
South Asian · 45/90,964 alleles
Filtering AF
0.0379%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0339%
Overall
0.0028%
45/1,607,796 alleles · ultra-rare
exomes 44/1,455,618 · genomes 1/152,178 · joint denominator
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
- HADH
- Protein
- p.Phe217=
- Coding
- c.651T>C
- MANE Select
- NM_005327
- dbSNP
- rs756177386
- Type
- single nucleotide variant
- Location
- chr4:108027702 (GRCh38)
- Gene constraint
- LOEUF 1.09 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.90 · 12 PDB
- Residue 217
- a turn
Similar variants
- HADH c.261+1G>A Pathogenic/Likely pathogenic ★★ same condition
- HADH c.262-2A>G Likely pathogenic ★★ same condition
- HADH c.709+2T>C Likely pathogenic ★★ same condition
- HADH p.Arg236Ter Pathogenic/Likely pathogenic ★★ same condition
- HADH p.Gly34Arg Likely pathogenic ★★ same condition
- HADH p.Ala239Ser Uncertain significance ★★ ⚠ same condition
- HADH p.Glu235Asp Uncertain significance ★★ ⚠ same condition
- HADH p.Gly34Ser Uncertain significance ★★ ⚠ 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/hadh-p-phe217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown