Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 59.3%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
hypercalcemia, infantile, 1
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 -14 | GERP -3.5 |
| Overall | ||
| CADD | 0.175 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
59.3%
East Asian · 26,616/44,856 alleles
Filtering AF
58.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 58.5%
Overall
24.4%
394,353/1,613,812 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 59.3% | 2 |
| African / African-American | 42% | 2 |
| South Asian | 34.1% | 3 |
| Admixed American | 27.1% | 4 |
| Remaining individualsnot grpmax-eligible | 26.5% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 23.3% | 4 |
| European (non-Finnish) | 21.3% | 5 |
| Middle Eastern | 20.9% | 5 |
| Finnishnot grpmax-eligible | 20.7% | 5 |
| Amishnot grpmax-eligible | 14.9% | 7 |
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
- CYP24A1
- Protein
- p.Pro375=
- Coding
- c.1125G>A
- MANE Select
- NM_000782
- dbSNP
- rs2296239
- Type
- single nucleotide variant
- Location
- chr20:54158989 (GRCh38)
- Gene constraint
- LOEUF 1.507 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.03
Disease context
hypercalcemia, infantile, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Autosomal recessive infantile hypercalcemia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- CYP24A1 p.Pro375Leu Uncertain significance ★★ ⚠ same residue
- CYP24A1 p.Arg159Gln Pathogenic/Likely pathogenic ★★ same condition
- CYP24A1 p.Arg159Trp Pathogenic/Likely pathogenic ★★ same condition
- CYP24A1 p.Arg223Ter Pathogenic ★★ same condition
- CYP24A1 p.Arg396Gln Pathogenic/Likely pathogenic ★★ same condition
- CYP24A1 p.Arg396Trp Pathogenic/Likely pathogenic ★★ same condition
- CYP24A1 p.Arg466Ter Pathogenic ★★ same condition
- CYP24A1 p.Gln347Ter Pathogenic/Likely pathogenic ★★ same condition
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/cyp24a1-p-pro375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown