# NM_001740.5(CALB2):c.630T>C (p.Asp210=)

https://sugi.bio/variant/calb2-p-asp210

## Summary

**CALB2 p.Asp210= (c.630T>C)** is classified **Likely benign** in CALB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). Very rare (popmax 0.00223%, eas).

**At a glance:** Likely benign · review: Single submitter · rsID rs2042560909 · 1 submitter · very rare (popmax 0.00223%, eas)

## For patients & families {#patients}

This is a change in the CALB2 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CALB2](https://sugi.bio/atlas/gene/CALB2/) |
| Protein change (HGVS p.) | p.Asp210= |
| Coding change (HGVS c.) | c.630T>C |
| MANE Select transcript | [NM_001740](https://www.ncbi.nlm.nih.gov/nuccore/NM_001740) |
| dbSNP | [rs2042560909](https://www.ncbi.nlm.nih.gov/snp/rs2042560909/) |
| Variant type | single nucleotide variant |
| Location | chr16:71385579-71385579 (GRCh38) |
| ClinVar | [VCV2613589](https://www.ncbi.nlm.nih.gov/clinvar/variation/2613589/) |

**All HGVS expressions:** `NC_000016.10:g.71385579T>C`, `NC_000016.9:g.71419482T>C`, `NM_001740.5:c.630T>C`, `NM_007088.4:c.536T>C`, `NR_027910.3:n.660T>C`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -10.077, GERP -3.71 — fast-evolving / accelerated position
- CADD: **PHRED 2.229**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (T>G, Δ0.75 acceptor loss), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.00223%** (eas) · FAF95 0.000247% · FAF99 0.000159% · 1/44,864 in the highest group · 8/1,461,808 alleles overall — very rare (popmax 0.00223%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| East Asian (grpmax) | 0.00223% | 44,864 |
| European (non-Finnish) | 0.000593% | 168,568 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**CALB2** population constraint: LOEUF 0.958, pLI 5.3217e-07, missense-Z -0.13079. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **210** lies in a binding site; the ef-hand 5 domain.

AlphaFold model confidence (whole protein): pLDDT 77.29, 1% of residues very-high.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-07-25.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2023-07-25 |

**Reported phenotype names (ClinVar):** not specified, AllHighlyPenetrant.

## Similar variants {#similar}

Related CALB2 variant pages (same residue, condition, or type): [CALB2 p.Ala115Val](/variant/calb2-p-ala115val), [CALB2 p.Ala129Val](/variant/calb2-p-ala129val), [CALB2 p.Arg145Gln](/variant/calb2-p-arg145gln), [CALB2 p.Arg145Leu](/variant/calb2-p-arg145leu), [CALB2 p.Arg161Gln](/variant/calb2-p-arg161gln), [CALB2 p.Arg258Cys](/variant/calb2-p-arg258cys), [CALB2 p.Asn231Ser](/variant/calb2-p-asn231ser), [CALB2 p.Asn236Ser](/variant/calb2-p-asn236ser).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 2613589). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*