# NM_005909.5(MAP1B):c.260_261del (p.Ser87fs)

https://sugi.bio/variant/map1b-p-ser87fs

## Summary

**MAP1B p.Ser87fs (c.260_261del)** is classified **Likely pathogenic** in MAP1B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-24). No gnomAD frequency available for this variant; Associated with periventricular nodular heterotopia 9.

**At a glance:** Likely pathogenic · review: No assertion criteria · rsID rs2478744517 · 1 submitter · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the MAP1B gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to periventricular nodular heterotopia 9.

*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:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0016394/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [MAP1B](https://sugi.bio/atlas/gene/MAP1B/) |
| Protein change (HGVS p.) | p.Ser87fs |
| Coding change (HGVS c.) | c.260_261del |
| MANE Select transcript | [NM_005909](https://www.ncbi.nlm.nih.gov/nuccore/NM_005909) |
| dbSNP | [rs2478744517](https://www.ncbi.nlm.nih.gov/snp/rs2478744517/) |
| Variant type | Microsatellite |
| Location | chr5:72115771-72115772 (GRCh38) |
| ClinVar | [VCV2664025](https://www.ncbi.nlm.nih.gov/clinvar/variation/2664025/) |

**All HGVS expressions:** `NC_000005.10:g.72115771CT[1]`, `NC_000005.9:g.71411598CT[1]`, `NM_005909.5:c.260_261del`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **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 11.258, GERP 5.81, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. the gene is **loss-of-function-intolerant** (LOEUF 0.105, pLI 1), supporting a loss-of-function disease mechanism. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 2 of 7**, so the transcript is predicted to undergo NMD.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no microsatellite variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*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}

**MAP1B** population constraint: LOEUF 0.105, pLI 1, missense-Z 3.9224. *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):

- **periventricular nodular heterotopia** — Strong (AD)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 46.18, 18% of residues very-high.

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

*Describes the biological roles of MAP1B (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:** MAP1B participates in disease-associated pathways. In Reactome, MAP1B is annotated in disease pathway(s) including **RSV-host interactions**.

**Disease mechanism (Reactome):** MAP1B loss or alteration is curated in [RSV-host interactions](https://reactome.org/content/detail/R-HSA-9833110).

### Pathways affected {#pathways}

MAP1B participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [RSV-host interactions](https://reactome.org/content/detail/R-HSA-9833110) | curated |

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

**Biological process:** neuron projection development, odontoblast differentiation.

## Clinical significance {#significance}

**Likely pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2023-11-24.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Zotz-Klimas Genetics Lab, MVZ Zotz Klimas | Likely pathogenic | no assertion criteria provided | clinical testing | 2023-11-24 |

## Associated conditions {#conditions}

[periventricular nodular heterotopia 9](https://sugi.bio/atlas/disease/periventricular-nodular-heterotopia-9/).

**Reported phenotype names (ClinVar):** Periventricular nodular heterotopia 9.

## Similar variants {#similar}

Related MAP1B variant pages (same residue, condition, or type): [MAP1B p.Arg1664Ter](/variant/map1b-p-arg1664ter), [MAP1B p.Arg303Ter](/variant/map1b-p-arg303ter), [MAP1B p.Arg85Ter](/variant/map1b-p-arg85ter), [MAP1B p.Arg999Ter](/variant/map1b-p-arg999ter), [MAP1B p.Lys781_Ile782insTer](/variant/map1b-p-lys781-ile782inster), [MAP1B p.Pro752fs](/variant/map1b-p-pro752fs), [MAP1B p.Arg1399Cys](/variant/map1b-p-arg1399cys), [MAP1B p.Glu1944Lys](/variant/map1b-p-glu1944lys).

### 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 2664025). 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.*