PHC1 p.Pro501=
c.1503T>G · VCV4915597
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00649%, amr)
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 -5.1 | GERP -2.1 |
| Overall | ||
| CADD | 4.713 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00649%
Admixed American · 3/46,228 alleles
Filtering AF
0.00172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000877%
Overall
0.000407%
3/736,486 alleles · very rare
exomes 0/599,704 · genomes 3/136,782 · joint denominator
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.Pro501=
- Coding
- c.1503T>G
- MANE Select
- NM_004426
- Type
- single nucleotide variant
- Location
- chr12:8932960 (GRCh38)
- Gene constraint
- LOEUF 0.322 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 51.06 · 1 PDB
- Residue 501
- the 'disordered' region
Similar variants
- PHC1 p.Arg876Gln Uncertain significance ★★ ⚠ same type
- PHC1 p.Arg876Trp Uncertain significance ★★ ⚠ same type
- PHC1 p.Arg939His Uncertain significance ★★ ⚠ same type
- PHC1 p.Glu684Ala Uncertain significance ★★ ⚠ same type
- PHC1 p.His629Asn Uncertain significance ★★ ⚠ same type
- PHC1 c.1106-60G>A Benign ★★ same type
- PHC1 c.114+191T>C Benign ★★ same type
- PHC1 c.1894-221A>G Benign ★★ 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-pro501 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown