# NM_001753.5(CAV1):c.330G>A (p.Pro110=)

https://sugi.bio/variant/cav1-p-pro110

## Summary

**CAV1 p.Pro110= (c.330G>A)** is classified **Likely benign** in CAV1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-12). Very rare (popmax 0.00334%, amr); Associated with pulmonary hypertension, primary, 3.

**At a glance:** Likely benign · review: Multiple submitters · rsID rs759074741 · 2 submitters · 1 linked condition · very rare (popmax 0.00334%, amr)

## For patients & families {#patients}

This is a change in the CAV1 gene that is classified as likely benign — not considered disease-causing, submitted by 2 submitters, and is linked to pulmonary hypertension, primary, 3.

*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.*

|  |  |
| --- | --- |
| Clinical trials | 2 registered for this condition — see ClinicalTrials.gov |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0024973/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CAV1](https://sugi.bio/atlas/gene/CAV1/) |
| Protein change (HGVS p.) | p.Pro110= |
| Coding change (HGVS c.) | c.330G>A |
| MANE Select transcript | [NM_001753](https://www.ncbi.nlm.nih.gov/nuccore/NM_001753) |
| dbSNP | [rs759074741](https://www.ncbi.nlm.nih.gov/snp/rs759074741/) |
| Variant type | single nucleotide variant |
| Location | chr7:116559080-116559080 (GRCh38) |
| ClinVar | [VCV1730066](https://www.ncbi.nlm.nih.gov/clinvar/variation/1730066/) |

**All HGVS expressions:** `NC_000007.13:g.116199134G>A`, `NC_000007.14:g.116559080G>A`, `NG_012051.1:g.39296G>A`, `NM_001172895.1:c.237G>A`, `NM_001172896.2:c.237G>A`, `NM_001172897.2:c.237G>A`, `NM_001753.5:c.330G>A`

## 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 -12.284, GERP -4.01 — fast-evolving / accelerated position
- CADD: **PHRED 0.008**. 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** — no allele at this position is in our SpliceAI release, either because it lies outside the scored MANE transcript scope or because every allele is below Δ0.2. We cannot tell which, so this claims neither; absence is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.00334%** (amr) · FAF95 0.000553% · FAF99 0.000312% · 2/59,942 in the highest group · 13/1,613,766 alleles overall — very rare (popmax 0.00334%, amr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Admixed American (grpmax) | 0.00334% | 29,971 |
| South Asian | 0.0011% | 91,072 |
| European (non-Finnish) | 0.000848% | 117,994 |

*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}

**CAV1** population constraint: LOEUF 0.967, pLI 0.014002, missense-Z 0.82289. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **pulmonary arterial hypertension** — Definitive (AD)
- **lipodystrophy** — Limited (AD)
- **congenital generalized lipodystrophy type 3** — Definitive (AR)
- **amyotrophic lateral sclerosis** — Limited (AD)

## Protein context {#protein}

Residue **110** lies in an α-helix.

AlphaFold model confidence (whole protein): pLDDT 78.60, 29% of residues very-high.

**1 experimental structure(s)** (PDB): [7SC0](https://www.rcsb.org/structure/7SC0).

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

*Describes the biological roles of CAV1 (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:** CAV1's established molecular role includes signaling receptor binding. In Reactome, CAV1 is annotated in disease pathway(s) including **SARS-CoV-1 targets host intracellular signalling and regulatory pathways**, **SARS-CoV-2 targets host intracellular signalling and regulatory pathways**.

**Disease mechanism (Reactome):** CAV1 loss or alteration is curated in [SARS-CoV-1 targets host intracellular signalling and regulatory pathways](https://reactome.org/content/detail/R-HSA-9735871), [SARS-CoV-2 targets host intracellular signalling and regulatory pathways](https://reactome.org/content/detail/R-HSA-9755779).

### Pathways affected {#pathways}

CAV1 participates in **27 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [SARS-CoV-1 targets host intracellular signalling and regulatory pathways](https://reactome.org/content/detail/R-HSA-9735871) | curated |
| ⚕ [SARS-CoV-2 targets host intracellular signalling and regulatory pathways](https://reactome.org/content/detail/R-HSA-9755779) | electronic |
| [Basigin interactions](https://reactome.org/content/detail/R-HSA-210991) | curated |
| [CDC42 GTPase cycle](https://reactome.org/content/detail/R-HSA-9013148) | curated |
| [Disassembly of the destruction complex and recruitment of AXIN to the membrane](https://reactome.org/content/detail/R-HSA-4641262) | curated |
| [Extra-nuclear estrogen signaling](https://reactome.org/content/detail/R-HSA-9009391) | curated |
| [FOXO-mediated transcription of cell cycle genes](https://reactome.org/content/detail/R-HSA-9617828) | curated |
| [NOSTRIN mediated eNOS trafficking](https://reactome.org/content/detail/R-HSA-203641) | curated |
| [RAC1 GTPase cycle](https://reactome.org/content/detail/R-HSA-9013149) | curated |
| [RAC2 GTPase cycle](https://reactome.org/content/detail/R-HSA-9013404) | curated |
| [RAC3 GTPase cycle](https://reactome.org/content/detail/R-HSA-9013423) | curated |
| [RHOA GTPase cycle](https://reactome.org/content/detail/R-HSA-8980692) | curated |
| [RHOB GTPase cycle](https://reactome.org/content/detail/R-HSA-9013026) | curated |
| [RHOC GTPase cycle](https://reactome.org/content/detail/R-HSA-9013106) | curated |
| [RHOD GTPase cycle](https://reactome.org/content/detail/R-HSA-9013405) | curated |
| [RHOF GTPase cycle](https://reactome.org/content/detail/R-HSA-9035034) | curated |
| [RHOG GTPase cycle](https://reactome.org/content/detail/R-HSA-9013408) | curated |
| [RHOH GTPase cycle](https://reactome.org/content/detail/R-HSA-9013407) | curated |
| [RHOJ GTPase cycle](https://reactome.org/content/detail/R-HSA-9013409) | curated |
| [RHOQ GTPase cycle](https://reactome.org/content/detail/R-HSA-9013406) | curated |
| [RND1 GTPase cycle](https://reactome.org/content/detail/R-HSA-9696273) | curated |
| [RND2 GTPase cycle](https://reactome.org/content/detail/R-HSA-9696270) | curated |
| [RND3 GTPase cycle](https://reactome.org/content/detail/R-HSA-9696264) | curated |
| [Thyroxine biosynthesis](https://reactome.org/content/detail/R-HSA-209968) | curated |
| [VEGFR2 mediated vascular permeability](https://reactome.org/content/detail/R-HSA-5218920) | curated |
| [eNOS activation](https://reactome.org/content/detail/R-HSA-203615) | curated |
| [Triglyceride catabolism](https://reactome.org/content/detail/R-HSA-163560) | electronic |

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

**Molecular function:** signaling receptor binding, enzyme binding, protein kinase binding, protein tyrosine kinase inhibitor activity, small GTPase binding, nitric-oxide synthase inhibitor activity.

**Biological process:** cellular response to starvation, response to bacterium, positive regulation of cholesterol efflux, receptor-mediated endocytosis of virus by host cell, regulation of blood coagulation, positive regulation of cell migration.

## Clinical significance {#significance}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2025-02-12.

**Submitter consensus:** unanimous (2/2 Likely benign).

**Submission history:** 2 submissions (2022–2025); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2022-04-19 |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2025-02-12 |

## Associated conditions {#conditions}

[pulmonary hypertension, primary, 3](https://sugi.bio/atlas/disease/pulmonary-hypertension-primary-3/).

**Reported phenotype names (ClinVar):** Pulmonary hypertension, primary, 3, Inborn genetic diseases.

## Similar variants {#similar}

Related CAV1 variant pages (same residue, condition, or type): [CAV1 p.Pro110Leu](/variant/cav1-p-pro110leu), [CAV1 c.30+3A>G](/variant/cav1-c-30-plus-3a-g), [CAV1 p.Arg101His](/variant/cav1-p-arg101his), [CAV1 p.Arg171His](/variant/cav1-p-arg171his), [CAV1 p.Gly83Ser](/variant/cav1-p-gly83ser), [CAV1 p.His79Arg](/variant/cav1-p-his79arg), [CAV1 p.Lys86Arg](/variant/cav1-p-lys86arg), [CAV1 p.Phe68Val](/variant/cav1-p-phe68val).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); 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 1730066). 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.*