# NM_001747.4(CAPG):c.24T>C (p.Ser8=)

https://sugi.bio/variant/capg-p-ser8

## Summary

**CAPG p.Ser8= (c.24T>C)** is classified **Likely benign** in CAPG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-15). Very rare (popmax 0.00267%, afr).

**At a glance:** Likely benign · review: Single submitter · 1 submitter · very rare (popmax 0.00267%, afr)

## For patients & families {#patients}

This is a change in the CAPG 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 | [CAPG](https://sugi.bio/atlas/gene/CAPG/) |
| Protein change (HGVS p.) | p.Ser8= |
| Coding change (HGVS c.) | c.24T>C |
| MANE Select transcript | [NM_001747](https://www.ncbi.nlm.nih.gov/nuccore/NM_001747) |
| Variant type | single nucleotide variant |
| Location | chr2:85401957-85401957 (GRCh38) |
| ClinVar | [VCV3484700](https://www.ncbi.nlm.nih.gov/clinvar/variation/3484700/) |

**All HGVS expressions:** `NC_000002.11:g.85629080A>G`, `NC_000002.12:g.85401957A>G`, `NG_095732.1:g.228A>G`, `NM_001256139.2:c.24T>C`, `NM_001256140.2:c.24T>C`, `NM_001320732.2:c.24T>C`, `NM_001320733.2:c.24T>C`, `NM_001320734.2:c.24T>C`, `NM_001747.4:c.24T>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 -5.576, GERP -4.43 — fast-evolving / accelerated position
- CADD: **PHRED 0.468**. 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 (A>T, Δ0.36 acceptor gain), 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 **0.00267%** (afr) · FAF95 0.000442% · FAF99 0.000166% · 2/75,044 in the highest group · 3/1,461,844 alleles overall — very rare (popmax 0.00267%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 0.00267% | 37,522 |
| Remaining individuals (not grpmax-eligible) | 0.0016% | 62,506 |

*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}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-08-15.

**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 | 2024-08-15 |

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

## Similar variants {#similar}

Related CAPG variant pages (same residue, condition, or type): [CAPG p.Ala206Thr](/variant/capg-p-ala206thr), [CAPG p.Ala229Thr](/variant/capg-p-ala229thr), [CAPG p.Ala241Gly](/variant/capg-p-ala241gly), [CAPG p.Ala81Pro](/variant/capg-p-ala81pro), [CAPG p.Arg112Trp](/variant/capg-p-arg112trp), [CAPG p.Arg149Cys](/variant/capg-p-arg149cys), [CAPG p.Arg149Ser](/variant/capg-p-arg149ser), [CAPG p.Arg153Trp](/variant/capg-p-arg153trp).

### 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 3484700). 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.*