HMGCR p.Phe206=
c.618C>T · rs768419319 · VCV3058447
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Conditions
1
HMGCR-related disorder
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 -4.6 | GERP -4.2 |
| Overall | ||
| CADD | 10.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,902 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000682%
11/1,613,922 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,902 |
| South Asian | 0.0011% | 91,076 |
| European (non-Finnish) | 0.000763% | 131,105 |
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
- HMGCR
- Protein
- p.Phe206=
- Coding
- c.618C>T
- MANE Select
- NM_000859
- dbSNP
- rs768419319
- Type
- single nucleotide variant
- Location
- chr5:75350103 (GRCh38)
- Gene constraint
- LOEUF 0.447 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.77 · 24 PDB
- Residue 206
- the ssd domain
Disease context
HMGCR-related disorder
Similar variants
- HMGCR c.*8G>A Benign same condition
- HMGCR p.Ser261= Likely benign same condition
- HMGCR p.Ser745= Likely benign same condition
- HMGCR p.Tyr311Ser Benign same condition
- HMGCR p.Arg641Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- HMGCR p.Arg443Gln Likely pathogenic ★ ⚠ same type
- HMGCR p.Arg840Ter Likely pathogenic ★ same type
- HMGCR p.Asp623Asn Likely pathogenic ★ ⚠ same type
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/hmgcr-p-phe206 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown