HPGD p.Val109=
c.327T>C · VCV3717959
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 0.7 | GERP -1.1, phastCons 0.95 |
| Overall | ||
| CADD | 7.467 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,922 alleles
Overall
0.000129%
2/1,547,008 alleles · very rare
exomes 0/1,394,786 · genomes 2/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,922 |
| African / African-American | 0.00136% | 73,634 |
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.Val109=
- Coding
- c.327T>C
- MANE Select
- NM_000860
- Type
- single nucleotide variant
- Location
- chr4:174508790 (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 109
- an α-helix
Similar variants
- 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
- HPGD p.Glu195Ala 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-val109 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown