PHC1 p.Pro440=
c.1320G>A · VCV4915596
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.341%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.016 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.28 | GERP -1.3 |
| Overall | ||
| CADD | 8.755 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.341%
African / African-American · 250/73,214 alleles
Filtering AF
0.307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.293%
Overall
0.0185%
292/1,577,104 alleles · rare
exomes 166/1,426,024 · genomes 126/151,080 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.341% | 293 |
| Remaining individualsnot grpmax-eligible | 0.0278% | 3,598 |
| Admixed American | 0.0276% | 3,629 |
| East Asian | 0.00225% | 44,444 |
| Finnishnot grpmax-eligible | 0.0016% | 62,600 |
| South Asian | 0.00111% | 89,926 |
| European (non-Finnish) | 0.000521% | 191,921 |
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.Pro440=
- Coding
- c.1320G>A
- MANE Select
- NM_004426
- Type
- single nucleotide variant
- Location
- chr12:8932777 (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 440
- 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-pro440 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown