# NM_014753.4(BMS1):c.260T>C (p.Val87Ala)

https://sugi.bio/variant/bms1-p-val87ala

## Summary

**BMS1 p.Val87Ala (c.260T>C)** is classified **Likely benign** in BMS1 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-11-05). AlphaMissense: likely pathogenic (0.8703); Rare (popmax 0.209%, eas).

**At a glance:** Likely benign · review: Single submitter · rsID rs201298233 · 2 submitters · AlphaMissense likely pathogenic · rare (popmax 0.209%, eas)

## For patients & families {#patients}

This is a change in the BMS1 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 | [BMS1](https://sugi.bio/atlas/gene/BMS1/) |
| Protein change (HGVS p.) | p.Val87Ala |
| Coding change (HGVS c.) | c.260T>C |
| MANE Select transcript | [NM_014753](https://www.ncbi.nlm.nih.gov/nuccore/NM_014753) |
| dbSNP | [rs201298233](https://www.ncbi.nlm.nih.gov/snp/rs201298233/) |
| Variant type | single nucleotide variant |
| Location | chr10:42785565-42785565 (GRCh38) |
| ClinVar | [VCV794146](https://www.ncbi.nlm.nih.gov/clinvar/variation/794146/) |

**All HGVS expressions:** `NC_000010.10:g.43281013T>C`, `NC_000010.11:g.42785565T>C`, `NG_046921.1:g.8060T>C`, `NM_014753.4:c.260T>C`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- AlphaMissense **likely pathogenic** (0.8703)
- REVEL 0.462 (indeterminate)
- SaProt LLR -11.506 (damaging) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense and SaProt both call this damaging; REVEL makes no call
- Conservation: phyloP 7.67, GERP 1.69, phastCons 1 — highly conserved (agrees)
- CADD: **PHRED 27.5**. 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.*
- Regional missense constraint: **o/e 0.77** across the covering region of the MANE Select transcript (42,784,395–42,791,745), spanning 7,350 bp. Chi-square p 3.4e-05. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code 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 **0.209%** (eas) · FAF95 0.175% · FAF99 0.162% · 94/44,880 in the highest group · 134/1,613,946 alleles overall — rare (popmax 0.209%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| East Asian (grpmax) | 0.209% | 477 |
| Remaining individuals (not grpmax-eligible) | 0.016% | 6,249 |
| Admixed American | 0.01% | 10,003 |
| South Asian | 0.00878% | 11,384 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.00338% | 29,600 |
| European (non-Finnish) | 0.00127% | 78,657 |

*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}

**BMS1** population constraint: LOEUF 0.507, pLI 0.50175, missense-Z 1.7727. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **87** lies in the bms1-type g domain; a β-strand.

AlphaFold model confidence (whole protein): pLDDT 72.04, 38% of residues very-high.

**3 experimental structure(s)** (PDB): [7MQ8](https://www.rcsb.org/structure/7MQ8), [7MQ9](https://www.rcsb.org/structure/7MQ9), [7MQA](https://www.rcsb.org/structure/7MQA).

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

*Describes the biological roles of BMS1 (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:** BMS1's established molecular role includes RNA binding. p.Val87Ala falls in the bms1-type g domain.


### Pathways affected {#pathways}

BMS1 participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Major pathway of rRNA processing in the nucleolus and cytosol](https://reactome.org/content/detail/R-HSA-6791226) | curated |
| [rRNA modification in the nucleus and cytosol](https://reactome.org/content/detail/R-HSA-6790901) | electronic |

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

**Molecular function:** RNA binding.

**Biological process:** ribosomal small subunit biogenesis.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2018-11-05.

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

**Submission history:** 2 submissions (2018–2019); 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 | 2018-11-05 |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2019-06-12 |

**Reported phenotype names (ClinVar):** not provided, BMS1-related disorder, BMS1-related condition, none provided, RECLASSIFIED - ADRA2C POLYMORPHISM, RECLASSIFIED - ADRB1 POLYMORPHISM.

## Similar variants {#similar}

Related BMS1 variant pages (same residue, condition, or type): [BMS1 p.Ala214Val](/variant/bms1-p-ala214val), [BMS1 p.Ala500=](/variant/bms1-p-ala500), [BMS1 p.Arg237His](/variant/bms1-p-arg237his), [BMS1 p.Arg38Trp](/variant/bms1-p-arg38trp), [BMS1 p.Arg863=](/variant/bms1-p-arg863), [BMS1 p.Asp768Asn](/variant/bms1-p-asp768asn), [BMS1 p.Glu1278=](/variant/bms1-p-glu1278), [BMS1 p.Ile942=](/variant/bms1-p-ile942).

### 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 794146). 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.*