CALCR p.Pro216=
c.648G>A · rs10269878 · VCV1285837
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 17.3%, afr) — too common for a highly-penetrant pathogenic allele
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 -4.7 | GERP -0.83 |
| Overall | ||
| CADD | 16.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
17.3%
African / African-American · 12,748/73,688 alleles
Filtering AF
17%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 16.9%
Overall
0.908%
14,541/1,600,908 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 17.3% | 6 |
| Admixed American | 1.19% | 84 |
| Remaining individualsnot grpmax-eligible | 1.17% | 85 |
| Middle Eastern | 0.786% | 127 |
| South Asian | 0.0483% | 2,069 |
| East Asian | 0.0338% | 2,955 |
| European (non-Finnish) | 0.0235% | 4,255 |
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
- CALCR
- Protein
- p.Pro216=
- Coding
- c.648G>A
- MANE Select
- NM_001742
- dbSNP
- rs10269878
- Type
- single nucleotide variant
- Location
- chr7:93460821 (GRCh38)
- Gene constraint
- LOEUF 1.039 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 32 PDB
Similar variants
- CALCR p.Val283Met Uncertain significance ★★ ⚠ same type
- CALCR c.1149+72A>G Benign ★★ same type
- CALCR c.1191+167C>A Benign ★★ same type
- CALCR c.206-113T>G Benign ★★ same type
- CALCR c.429+37T>C Benign ★★ same type
- CALCR c.51+105C>T Benign ★★ same type
- CALCR c.521+53C>T Benign ★★ same type
- CALCR c.522-1226A>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/calcr-p-pro216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown