# NM_144691.4(CAPN12):c.2079C>T (p.His693=)

https://sugi.bio/variant/capn12-p-his693

## Summary

**CAPN12 p.His693= (c.2079C>T)** is classified **Likely benign** in CAPN12 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-01). Rare (popmax 0.211%, nfe).

**At a glance:** Likely benign · review: Multiple submitters · rsID rs187740309 · 3 submitters · rare (popmax 0.211%, nfe)

## For patients & families {#patients}

This is a change in the CAPN12 gene that is classified as likely benign — not considered disease-causing, submitted by 3 submitters.

*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 | [CAPN12](https://sugi.bio/atlas/gene/CAPN12/) |
| Protein change (HGVS p.) | p.His693= |
| Coding change (HGVS c.) | c.2079C>T |
| MANE Select transcript | [NM_004924](https://www.ncbi.nlm.nih.gov/nuccore/NM_004924) (variant reported on NM_144691) |
| dbSNP | [rs187740309](https://www.ncbi.nlm.nih.gov/snp/rs187740309/) |
| Variant type | single nucleotide variant |
| Location | chr19:38731019-38731019 (GRCh38) |
| ClinVar | [VCV735155](https://www.ncbi.nlm.nih.gov/clinvar/variation/735155/) |

**All HGVS expressions:** `NC_000019.10:g.38731019G>A`, `NC_000019.9:g.39221659G>A`, `NG_007082.2:g.88333G>A`, `NM_001322033.2:c.*1587G>A`, `NM_001411143.1:c.*1587G>A`, `NM_004924.6:c.*1587G>A`, `NM_144691.4:c.2079C>T`

## 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 5.786, GERP 2.15, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 2.73**. 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: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **0.211%** (nfe) · FAF95 0.204% · FAF99 0.201% · 2,426/1,149,072 in the highest group · 2,656/1,554,138 alleles overall — rare (popmax 0.211%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| European (non-Finnish) (grpmax) | 0.211% | 474 |
| Remaining individuals (not grpmax-eligible) | 0.138% | 725 |
| Admixed American | 0.107% | 936 |
| Finnish (not grpmax-eligible) | 0.097% | 1,031 |
| African / African-American | 0.0463% | 2,158 |
| Middle Eastern | 0.0167% | 5,980 |

*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.*

## Clinical significance {#significance}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2023-12-01.

**Submitter consensus:** unanimous (3/3 Likely benign).

**Submission history:** 3 submissions (2018–2023); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2018-05-30 |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2019-05-07 |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2023-12-01 |

**Reported phenotype names (ClinVar):** not provided, CAPN12-related disorder, CAPN12-related condition, none provided.

### 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 735155). 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.*