CALCR p.His331=
c.993T>C · rs140388547 · VCV3049696
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.735%, eas)
Conditions
1
CALCR-related disorder
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 -0.67 | GERP -5.5 |
| Overall | ||
| CADD | 2.992 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.735%
East Asian · 330/44,890 alleles
Filtering AF
0.67%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.644%
Overall
0.022%
355/1,614,188 alleles · rare
exomes 335/1,461,844 · genomes 20/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.735% | 136 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,929 |
| South Asian | 0.00329% | 30,360 |
| Admixed American | 0.00167% | 60,018 |
| European (non-Finnish) | 0.0011% | 90,770 |
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.His331=
- Coding
- c.993T>C
- MANE Select
- NM_001742
- dbSNP
- rs140388547
- Type
- single nucleotide variant
- Location
- chr7:93436108 (GRCh38)
- Gene constraint
- LOEUF 1.039 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 32 PDB
Disease context
CALCR-related disorder
Similar variants
- CALCR p.Val283Met Uncertain significance ★★ ⚠ same condition
- CALCR p.Leu176Phe Uncertain significance ★ ⚠ same condition
- CALCR p.Glu457Lys Likely benign same condition
- CALCR p.Ile160Val Likely benign same condition
- CALCR p.Ser175Asn Benign same condition
- CALCR p.Ser27= Likely benign same condition
- CALCR c.1149+72A>G Benign ★★ same type
- CALCR c.1191+167C>A 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-his331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown