HPGD p.Ala166=
c.498G>A · rs200828629 · VCV2192508
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0533%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.85 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.70 | loss · gain 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 23.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0533%
Admixed American · 32/59,982 alleles
Filtering AF
0.0388%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0339%
Overall
0.00292%
47/1,607,170 alleles · ultra-rare
exomes 36/1,454,932 · genomes 11/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0533% | 1,874 |
| East Asian | 0.00669% | 14,941 |
| South Asian | 0.0033% | 30,318 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,129 |
| African / African-American | 0.00134% | 74,832 |
| European (non-Finnish) | 0.000511% | 195,639 |
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
- HPGD
- Protein
- p.Ala166=
- Coding
- c.498G>A
- MANE Select
- NM_000860
- dbSNP
- rs200828629
- Type
- single nucleotide variant
- Location
- chr4:174495548 (GRCh38)
- Gene constraint
- LOEUF 1.28 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.82 · 6 PDB
- Residue 166
- an α-helix
Similar variants
- HPGD p.Ala166Val Uncertain significance ★ ⚠ same residue
- HPGD c.218-1G>A Pathogenic ★★ same type
- HPGD c.324+5G>A Pathogenic ★★ same type
- HPGD c.421+1G>T Pathogenic ★★ same type
- HPGD p.Ala140Pro Pathogenic ★★ same type
- HPGD p.Gln68Ter Pathogenic ★★ same type
- HPGD c.*157A>G Uncertain significance ★★ same type
- HPGD p.Asn95Ser Uncertain significance ★★ ⚠ 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/hpgd-p-ala166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown