HMGCR p.Ser261=
c.783T>A · rs1055477224 · VCV3034997
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00268%, afr)
Conditions
1
HMGCR-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.48 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.36 | gain · loss 0.20 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.63 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 16.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00268%
African / African-American · 2/74,756 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00118%
19/1,610,976 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00268% | 37,378 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,352 |
| European (non-Finnish) | 0.00136% | 73,689 |
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.Ser261=
- Coding
- c.783T>A
- MANE Select
- NM_000859
- dbSNP
- rs1055477224
- Type
- single nucleotide variant
- Location
- chr5:75350791 (GRCh38)
- Gene constraint
- LOEUF 0.447 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.77 · 24 PDB
Disease context
HMGCR-related disorder
Similar variants
- HMGCR c.*8G>A Benign same condition
- HMGCR p.Phe206= 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-ser261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown