# NM_001747.4(CAPG):c.332del (p.Pro111fs)

https://sugi.bio/variant/capg-p-pro111fs

## Summary

**CAPG p.Pro111fs (c.332del)** is classified **Benign** in CAPG (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Rare (popmax 0.988%, afr).

**At a glance:** Benign · review: Single submitter · rsID rs372064925 · 1 submitter · rare (popmax 0.988%, afr)

## For patients & families {#patients}

This is a change in the CAPG gene that is classified as 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 | [CAPG](https://sugi.bio/atlas/gene/CAPG/) |
| Protein change (HGVS p.) | p.Pro111fs |
| Coding change (HGVS c.) | c.332del |
| MANE Select transcript | [NM_001747](https://www.ncbi.nlm.nih.gov/nuccore/NM_001747) |
| dbSNP | [rs372064925](https://www.ncbi.nlm.nih.gov/snp/rs372064925/) |
| Variant type | Deletion |
| Location | chr2:85401548-85401548 (GRCh38) |
| ClinVar | [VCV785969](https://www.ncbi.nlm.nih.gov/clinvar/variation/785969/) |

**All HGVS expressions:** `NC_000002.11:g.85628673del`, `NC_000002.12:g.85401550del`, `NM_001256139.2:c.332del`, `NM_001256140.2:c.332del`, `NM_001320732.2:c.332del`, `NM_001320733.2:c.332del`, `NM_001320734.2:c.332del`, `NM_001747.4:c.332del`

## 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 -9.653, GERP -4.67 — fast-evolving / accelerated position
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.947, pLI 5.535e-08. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 4 of 10**, so the transcript is predicted to undergo NMD.
- CADD: **PHRED 34.0**. 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 assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.988%** (afr) · FAF95 0.929% · FAF99 0.905% · 741/75,010 in the highest group · 780/1,614,054 alleles overall — rare (popmax 0.988%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 0.988% | 101 |
| Remaining individuals (not grpmax-eligible) | 0.0368% | 2,718 |
| Admixed American | 0.0233% | 4,287 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 8.47e-05% | 1,179,967 |

*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}

**CAPG** population constraint: LOEUF 0.947, pLI 5.535e-08, missense-Z 0.63187. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 86.89, 56% of residues very-high.

**2 experimental structure(s)** (PDB): [1J72](https://www.rcsb.org/structure/1J72), [1JHW](https://www.rcsb.org/structure/1JHW) — incl. mutant structure 1J72.

## What this gene does {#gene-function}

*Describes the biological roles of CAPG (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** CAPG's established molecular role includes protein domain specific binding.


### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** protein domain specific binding, protein-containing complex binding, cadherin binding.

## Clinical significance {#significance}

**Benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2019-12-31.

**Submitter consensus:** unanimous (1/1 Benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2019-12-31 |

**Reported phenotype names (ClinVar):** not provided, none provided.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 2026-10-14); 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 785969). 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.*