HPGD p.Ser174=
c.522T>C · rs146971052 · VCV742091
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.299%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.42 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.82 | GERP -3.3, phastCons 0.97 |
| Overall | ||
| CADD | 8.271 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.299%
African / African-American · 224/75,000 alleles
Filtering AF
0.267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.254%
Overall
0.0152%
246/1,613,188 alleles · rare
exomes 123/1,460,972 · genomes 123/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.299% | 335 |
| Admixed American | 0.0183% | 5,451 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,941 |
| European (non-Finnish) | 0.00017% | 589,671 |
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.Ser174=
- Coding
- c.522T>C
- MANE Select
- NM_000860
- dbSNP
- rs146971052
- Type
- single nucleotide variant
- Location
- chr4:174493291 (GRCh38)
- Gene constraint
- LOEUF 1.28 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.82 · 6 PDB
Similar variants
- HPGD p.Ser174Arg 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-ser174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown