CALCA p.Leu126=
c.378G>A · rs35425520 · VCV768429
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.325%, afr)
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 0.51 | GERP -0.64 |
| Overall | ||
| CADD | 5.068 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.325%
African / African-American · 244/75,022 alleles
Filtering AF
0.292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.279%
Overall
0.0171%
276/1,614,146 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.325% | 307 |
| Admixed American | 0.0267% | 3,751 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,809 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.0011% | 91,068 |
| European (non-Finnish) | 8.47e-05% | 1,180,036 |
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
- CALCA
- Protein
- p.Leu126=
- Coding
- c.378G>A
- MANE Select
- NM_001741
- dbSNP
- rs35425520
- Type
- single nucleotide variant
- Location
- chr11:14968847 (GRCh38)
- Gene constraint
- LOEUF 1.186 · pLI 0.13 (gnomAD)
- Structure
- AlphaFold pLDDT 64.12 · 6 PDB
- Residue 126
- the 'disordered' region
Similar variants
- CALCA p.Phe106= Benign ★★ same type
- CALCA p.Ala118Val Uncertain significance ★ same type
- CALCA p.Ala11Thr Uncertain significance ★ ⚠ same type
- CALCA p.Ala31Ser Uncertain significance ★ ⚠ same type
- CALCA p.Ala47Pro Uncertain significance ★ ⚠ same type
- CALCA p.Ala47Val Uncertain significance ★ ⚠ same type
- CALCA p.Arg123Cys Uncertain significance ★ same type
- CALCA p.Arg84Gln 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/calca-p-leu126 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown