# NM_001375505.1(MAP2):c.5067G>T (p.Gly1689=)

https://sugi.bio/variant/map2-p-gly1689

## Summary

**MAP2 p.Gly1689= (c.5067G>T)** is classified **Benign** in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-10). Rare (popmax 0.72%, sas).

**At a glance:** Benign · review: Single submitter · rsID rs541515893 · 1 submitter · rare (popmax 0.72%, sas)

## For patients & families {#patients}

This is a change in the MAP2 gene that is classified as 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 | [MAP2](https://sugi.bio/atlas/gene/MAP2/) |
| Protein change (HGVS p.) | p.Gly1689= |
| Coding change (HGVS c.) | c.5067G>T |
| MANE Select transcript | [NM_001375505](https://www.ncbi.nlm.nih.gov/nuccore/NM_001375505) |
| dbSNP | [rs541515893](https://www.ncbi.nlm.nih.gov/snp/rs541515893/) |
| Variant type | single nucleotide variant |
| Location | chr2:209710248-209710248 (GRCh38) |
| ClinVar | [VCV733331](https://www.ncbi.nlm.nih.gov/clinvar/variation/733331/) |

**All HGVS expressions:** `NC_000002.11:g.210574972G>T`, `NC_000002.12:g.209710248G>T`, `NG_052836.1:g.291202G>T`, `NM_001039538.2:c.1170G>T`, `NM_001363910.2:c.5055G>T`, `NM_001363911.2:c.5055G>T`, `NM_001363913.2:c.999G>T`, `NM_001375474.1:c.1170G>T`, `NM_001375493.1:c.999G>T`, `NM_001375494.1:c.999G>T`, `NM_001375495.1:c.1341G>T`, `NM_001375496.1:c.1167G>T`, `NM_001375497.1:c.996G>T`, `NM_001375498.1:c.1335G>T`, `NM_001375499.1:c.999G>T`, `NM_001375500.1:c.5055G>T`, `NM_001375501.1:c.5313G>T`, `NM_001375502.1:c.5064G>T`, `NM_001375503.1:c.5295G>T`, `NM_001375504.1:c.5238G>T`, `NM_001375505.1:c.5067G>T`, `NM_001375506.1:c.5064G>T`, `NM_001375507.1:c.5052G>T`, `NM_001375508.1:c.999G>T`, `NM_001375509.1:c.1224G>T`, `NM_001375510.1:c.1341G>T`, `NM_001375526.1:c.5067G>T`, `NM_001375527.1:c.5064G>T`, `NM_001375528.1:c.5055G>T`, `NM_001375529.1:c.996G>T`, `NM_001375530.1:c.996G>T`, `NM_001375531.1:c.5310G>T`, `NM_001375532.1:c.996G>T`, `NM_001375533.1:c.996G>T`, `NM_001375534.1:c.5067G>T`, `NM_001375535.1:c.1242G>T`, `NM_001375536.1:c.1341G>T`, `NM_001375537.1:c.5313G>T`, `NM_001375538.1:c.1338G>T`, `NM_001375539.1:c.5301G>T`, `NM_001375540.1:c.1335G>T`, `NM_001375541.1:c.1134G>T`, `NM_001375542.1:c.993G>T`, `NM_001375543.1:c.5064G>T`, `NM_001375544.1:c.5064G>T`, `NM_001375545.1:c.5052G>T`, `NM_001375546.1:c.5052G>T`, `NM_001375548.1:c.5052G>T`, `NM_001375551.1:c.4593G>T`, `NM_001375552.1:c.4593G>T`, `NM_001375553.1:c.870G>T`, `NM_001375554.1:c.870G>T`, `NM_001375555.1:c.4593G>T`, `NM_001375556.1:c.4593G>T`, `NM_001375557.1:c.4593G>T`, `NM_001375558.1:c.4590G>T`, `NM_001375559.1:c.4590G>T`, `NM_001375583.1:c.999G>T`, `NM_002374.4:c.5067G>T`, `NM_031845.3:c.999G>T`, `NM_031847.3:c.999G>T`, `NR_164694.1:n.902G>T`, `NR_164695.1:n.920G>T`, `NR_164696.1:n.917G>T`, `NR_164697.1:n.920G>T`, `NR_164698.1:n.1091G>T`, `NR_164699.1:n.858G>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 and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **donor gain** (Δ 0.47) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP -0.178, GERP -1.09, phastCons 0.063 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 15.02**. 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 deltas (raw): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.47**. Largest is donor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.47**.
- Population frequency (gnomAD v4.1): grpmax **0.72%** (sas) · FAF95 0.673% · FAF99 0.654% · 624/86,692 in the highest group · 647/1,569,180 alleles overall — rare (popmax 0.72%, sas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| South Asian (grpmax) | 0.72% | 139 |
| Middle Eastern | 0.0333% | 3,001 |
| Remaining individuals (not grpmax-eligible) | 0.0263% | 3,801 |
| African / African-American | 0.00678% | 14,749 |

*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.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 86.07, 78% of residues very-high.

**40 experimental structure(s)** (PDB): [1B59](https://www.rcsb.org/structure/1B59), [1B6A](https://www.rcsb.org/structure/1B6A), [1BN5](https://www.rcsb.org/structure/1BN5), [1BOA](https://www.rcsb.org/structure/1BOA), [1KQ0](https://www.rcsb.org/structure/1KQ0), [1KQ9](https://www.rcsb.org/structure/1KQ9).

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

*Describes the biological roles of MAP2 (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:** MAP2's established molecular role includes RNA binding.


### Pathways affected {#pathways}

MAP2 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Inactivation, recovery and regulation of the phototransduction cascade](https://reactome.org/content/detail/R-HSA-2514859) | curated |

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

**Molecular function:** RNA binding, aminopeptidase activity, metalloexopeptidase activity.

**Biological process:** regulation of translational initiation, protein processing.

## Clinical significance {#significance}

**Benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2018-04-10.

**Submitter consensus:** unanimous (1/1 Benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2018-04-10 |

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

## Similar variants {#similar}

Related MAP2 variant pages (same residue, condition, or type): [MAP2 p.Ala1074Thr](/variant/map2-p-ala1074thr), [MAP2 p.Ala752Ser](/variant/map2-p-ala752ser), [MAP2 p.Arg1715His](/variant/map2-p-arg1715his), [MAP2 p.Val1359Ala](/variant/map2-p-val1359ala), [MAP2 p.Ala414Ser](/variant/map2-p-ala414ser), [MAP2 p.Asp679=](/variant/map2-p-asp679), [MAP2 p.Gln1760=](/variant/map2-p-gln1760), [MAP2 p.Glu1129=](/variant/map2-p-glu1129).

### 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 733331). 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.*