PHC1 p.Val73=
c.219C>A · rs201150017 · VCV3037744
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0229%, nfe)
Conditions
1
PHC1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 0.83, phastCons 1 |
| Overall | ||
| CADD | 9.882 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0229%
European (non-Finnish) · 268/1,170,226 alleles
Filtering AF
0.0206%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.0177%
282/1,596,622 alleles · ultra-rare
exomes 271/1,444,434 · genomes 11/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0229% | 4,367 |
| Remaining individualsnot grpmax-eligible | 0.0146% | 6,867 |
| African / African-American | 0.00669% | 14,939 |
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
- PHC1
- Protein
- p.Val73=
- Coding
- c.219C>A
- MANE Select
- NM_004426
- dbSNP
- rs201150017
- Type
- single nucleotide variant
- Location
- chr12:8919860 (GRCh38)
- Gene constraint
- LOEUF 0.322 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 51.06 · 1 PDB
Disease context
PHC1-related disorder
Similar variants
- PHC1 p.Val73Ile Uncertain significance ★ ⚠ same residue
- PHC1 c.2253+8C>T Likely benign same condition
- PHC1 p.Gln408= Likely benign same condition
- PHC1 p.Gly927= Likely benign same condition
- PHC1 p.Ser303fs Likely pathogenic ★ same condition
- PHC1 p.Arg876Gln Uncertain significance ★★ ⚠ same type
- PHC1 p.Arg876Trp Uncertain significance ★★ ⚠ same type
- PHC1 p.Arg939His 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/phc1-p-val73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown