CALCA p.Arg123Cys
c.367C>T · rs782436716 · VCV3136640
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.353 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.7 | GERP 2.3 |
| Overall | ||
| CADD | 17.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,080 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000867%
14/1,613,992 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,770 |
| Admixed American | 0.00333% | 30,007 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00133% | 74,920 |
| European (non-Finnish) | 0.000508% | 196,671 |
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.Arg123Cys
- Coding
- c.367C>T
- MANE Select
- NM_001741 · reported on NM_001033953
- dbSNP
- rs782436716
- Type
- single nucleotide variant
- Location
- chr11:14967715 (GRCh38)
- Gene constraint
- LOEUF 1.186 · pLI 0.13 (gnomAD)
- Structure
- AlphaFold pLDDT 64.12 · 6 PDB
- Residue 123
- a UniProt-annotated variant site (in); 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.Arg84Gln Uncertain significance ★ ⚠ same type
- CALCA p.Arg84Pro 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-arg123cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown