# NM_001711.6(BGN):c.165C>T (p.Val55=)

https://sugi.bio/variant/bgn-p-val55

## Summary

**BGN p.Val55= (c.165C>T)** is classified **Likely benign** in BGN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-20). Ultra-rare (popmax 0.0118%, eas).

**At a glance:** Likely benign · review: Multiple submitters · 2 submitters · ultra-rare (popmax 0.0118%, eas)

## For patients & families {#patients}

This is a change in the BGN gene that is classified as likely benign — not considered disease-causing, submitted by 2 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 | [BGN](https://sugi.bio/atlas/gene/BGN/) |
| Protein change (HGVS p.) | p.Val55= |
| Coding change (HGVS c.) | c.165C>T |
| MANE Select transcript | [NM_001711](https://www.ncbi.nlm.nih.gov/nuccore/NM_001711) |
| Variant type | single nucleotide variant |
| Location | chrX:153504796-153504796 (GRCh38) |
| ClinVar | [VCV3685171](https://www.ncbi.nlm.nih.gov/clinvar/variation/3685171/) |

**All HGVS expressions:** `NC_000023.10:g.152770254C>T`, `NC_000023.11:g.153504796C>T`, `NG_015961.1:g.14844C>T`, `NM_001711.6:c.165C>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 -0.039, GERP -3.77, phastCons 0.221 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 2.804**. 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 (C>A, Δ0.20 donor 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 **0.0118%** (eas) · FAF95 0.00395% · FAF99 0.00235% · 4/33,850 in the highest group · 5/1,211,710 alleles overall — ultra-rare (popmax 0.0118%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| East Asian (grpmax) | 0.0118% | 8,463 |
| Remaining individuals (not grpmax-eligible) | 0.0021% | 47,653 |

*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}


Curated gene–disease validity (ClinGen):

- **Meester-Loeys syndrome** — Strong (XL)
- **familial thoracic aortic aneurysm and aortic dissection** — Limited (AD)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 85.72, 78% of residues very-high.

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

*Describes the biological roles of BGN (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:** BGN participates in disease-associated pathways. In Reactome, BGN is annotated in disease pathway(s) including **Defective B3GALT6 causes EDSP2 and SEMDJL1**, **Defective B3GAT3 causes JDSSDHD**.

**Disease mechanism (Reactome):** BGN loss or alteration is curated in [Defective B3GALT6 causes EDSP2 and SEMDJL1](https://reactome.org/content/detail/R-HSA-4420332), [Defective B3GAT3 causes JDSSDHD](https://reactome.org/content/detail/R-HSA-3560801), [Defective B4GALT7 causes EDS, progeroid type](https://reactome.org/content/detail/R-HSA-3560783).

### Pathways affected {#pathways}

BGN participates in **11 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Defective B3GALT6 causes EDSP2 and SEMDJL1](https://reactome.org/content/detail/R-HSA-4420332) | curated |
| ⚕ [Defective B3GAT3 causes JDSSDHD](https://reactome.org/content/detail/R-HSA-3560801) | curated |
| ⚕ [Defective B4GALT7 causes EDS, progeroid type](https://reactome.org/content/detail/R-HSA-3560783) | curated |
| ⚕ [Defective CHST14 causes EDS, musculocontractural type](https://reactome.org/content/detail/R-HSA-3595174) | curated |
| ⚕ [Defective CHST3 causes SEDCJD](https://reactome.org/content/detail/R-HSA-3595172) | curated |
| ⚕ [Defective CHSY1 causes TPBS](https://reactome.org/content/detail/R-HSA-3595177) | curated |
| [CS-GAG biosynthesis](https://reactome.org/content/detail/R-HSA-2022870) | curated |
| [CS/DS degradation](https://reactome.org/content/detail/R-HSA-2024101) | curated |
| [DS-GAG biosynthesis](https://reactome.org/content/detail/R-HSA-2022923) | curated |
| [Glycosaminoglycan-protein linkage region biosynthesis](https://reactome.org/content/detail/R-HSA-1971475) | curated |
| [ECM proteoglycans](https://reactome.org/content/detail/R-HSA-3000178) | electronic |

## Clinical significance {#significance}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2024-08-20.

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

**Submission history:** 2 submissions (2023–2024); 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 | 2024-08-20 |
| Blueprint Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2023-08-14 |

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

## Similar variants {#similar}

Related BGN variant pages (same residue, condition, or type): [BGN p.Val55Leu](/variant/bgn-p-val55leu), [BGN c.770+1G>A](/variant/bgn-c-770-plus-1g-a), [BGN p.Gln75Ter](/variant/bgn-p-gln75ter), [BGN p.Trp25Ter](/variant/bgn-p-trp25ter), [BGN c.909+4A>G](/variant/bgn-c-909-plus-4a-g), [BGN p.Ala330Asp](/variant/bgn-p-ala330asp), [BGN p.Ala330Pro](/variant/bgn-p-ala330pro), [BGN p.Ala41Ser](/variant/bgn-p-ala41ser).

### 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 3685171). 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.*